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Open AccessArticle Study of Adsorption and Desorption Performances of Zr-Based Metal–Organic Frameworks Using Paper Spray Mass Spectrometry
by , , and
Materials 2017, 10(7), 769; doi:10.3390/ma10070769
Received: 11 June 2017 / Revised: 3 July 2017 / Accepted: 4 July 2017 / Published: 8 July 2017
Viewed by 238 | PDF Full-text (3650 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The dynamic pore systems and high surface areas of flexible metal–organic framework materials make them excellent candidates to be used in different kinds of adsorption processes. However, the adsorption and desorption behaviors of therapeutic drugs on metal–organic frameworks in solution are not fully
[...] Read more.
The dynamic pore systems and high surface areas of flexible metal–organic framework materials make them excellent candidates to be used in different kinds of adsorption processes. However, the adsorption and desorption behaviors of therapeutic drugs on metal–organic frameworks in solution are not fully developed. Here, we systematically investigated the adsorption and desorption behaviors of a typical therapeutic drug, verapamil, over several Zr-based metal–organic frameworks [e.g., Zr-FUM, UiO-66(Zr), UiO-66(Zr)-NH2 and UiO-66(Zr)-2COOH] as well as ZrO2 in an acetonitrile solution by using paper spray mass spectrometry. In contrast to other materials, UiO-66(Zr)-2COOH demonstrated a superior adsorption performance to verapamil due to their strong acid-base and/or hydrogen-bond interactions, and the adsorption process fitted well with the pseudo-second-order kinetic model. As verapamil-adsorbed materials were used for desorption experiments, ZrO2 demonstrated the most favorable desorption performance, whereas UiO-66(Zr)-2COOH yielded the poorest desorption capability. These Zr-based materials had also been coated at the surface with filter papers for the analysis of various drugs and proteins in the process of paper spray mass spectrometry. The results demonstrated that among the studied materials, ZrO2-coated paper gave the most favorable desorption performance as a pure drug solution, whereas the paper from UiO-66(Zr) demonstrated the optimal capability in the analyses of therapeutic drugs in a complex matrix (e.g., blood) and a protein (e.g., myoglobin). Full article
(This article belongs to the Special Issue Metal Organic Framework Materials)
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Open AccessFeature PaperReview Nanomaterials as Assisted Matrix of Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for the Analysis of Small Molecules
by , , , , and
Nanomaterials 2017, 7(4), 87; doi:10.3390/nano7040087
Received: 26 March 2017 / Revised: 12 April 2017 / Accepted: 19 April 2017 / Published: 21 April 2017
Viewed by 792 | PDF Full-text (2460 KB) | HTML Full-text | XML Full-text
Abstract
Matrix-assisted laser desorption/ionization (MALDI), a soft ionization method, coupling with time-of-flight mass spectrometry (TOF MS) has become an indispensible tool for analyzing macromolecules, such as peptides, proteins, nucleic acids and polymers. However, the application of MALDI for the analysis of small molecules (<700
[...] Read more.
Matrix-assisted laser desorption/ionization (MALDI), a soft ionization method, coupling with time-of-flight mass spectrometry (TOF MS) has become an indispensible tool for analyzing macromolecules, such as peptides, proteins, nucleic acids and polymers. However, the application of MALDI for the analysis of small molecules (<700 Da) has become the great challenge because of the interference from the conventional matrix in low mass region. To overcome this drawback, more attention has been paid to explore interference-free methods in the past decade. The technique of applying nanomaterials as matrix of laser desorption/ionization (LDI), also called nanomaterial-assisted laser desorption/ionization (nanomaterial-assisted LDI), has attracted considerable attention in the analysis of low-molecular weight compounds in TOF MS. This review mainly summarized the applications of different types of nanomaterials including carbon-based, metal-based and metal-organic frameworks as assisted matrices for LDI in the analysis of small biological molecules, environmental pollutants and other low-molecular weight compounds. Full article
(This article belongs to the Special Issue Nanomaterials for Mass Spectrometry Applications)
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Open AccessArticle A Nanostructured Matrices Assessment to Study Drug Distribution in Solid Tumor Tissues by Mass Spectrometry Imaging
by , , , , , , , , , , , , and
Nanomaterials 2017, 7(3), 71; doi:10.3390/nano7030071
Received: 6 February 2017 / Revised: 13 March 2017 / Accepted: 16 March 2017 / Published: 21 March 2017
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Abstract
The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all cells in an adequate enough concentration to eradicate the tumor. Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) is one of the most promising imaging techniques
[...] Read more.
The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all cells in an adequate enough concentration to eradicate the tumor. Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) is one of the most promising imaging techniques that enables the simultaneous visualization of multiple compounds inside tissues. The choice of a suitable matrix constitutes a critical aspect during the development of a MALDI-MSI protocol since the matrix ionization efficiency changes depending on the analyte structure and its physico-chemical properties. The objective of this study is the improvement of the MALDI-MSI technique in the field of pharmacology; developing specifically designed nanostructured surfaces that allow the imaging of different drugs with high sensitivity and reproducibility. Among several nanomaterials, we tested the behavior of gold and titanium nanoparticles, and halloysites and carbon nanotubes as possible matrices. All nanomaterials were firstly screened by co-spotting them with drugs on a MALDI plate, evaluating the drug signal intensity and the signal-to-noise ratio. The best performing matrices were tested on control tumor slices, and were spotted with drugs to check the ion suppression effect of the biological matrix. Finally; the best nanomaterials were employed in a preliminary drug distribution study inside tumors from treated mice. Full article
(This article belongs to the Special Issue Nanomaterials for Mass Spectrometry Applications)
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Open AccessArticle MicroRNA MultiTool: A Software for Identifying Modified and Unmodified Human microRNA Using Mass Spectrometry
by , and
Non-Coding RNA 2017, 3(1), 13; doi:10.3390/ncrna3010013
Received: 31 December 2016 / Revised: 10 March 2017 / Accepted: 10 March 2017 / Published: 16 March 2017
Viewed by 251 | PDF Full-text (3003 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
microRNA (miRNA) are short endogenous non-coding RNA that play a crucial role in post-transcriptional gene regulation and have been implicated in the initiation and progression of 160+ human diseases. Excellent analytical methods have been developed for the measurement of miRNA by mass spectrometry.
[...] Read more.
microRNA (miRNA) are short endogenous non-coding RNA that play a crucial role in post-transcriptional gene regulation and have been implicated in the initiation and progression of 160+ human diseases. Excellent analytical methods have been developed for the measurement of miRNA by mass spectrometry. However, interpretation of mass spectrometric data has been an incapacitating bottleneck in miRNA identification. This study details the development of MicroRNA MultiTool, a software for the identification of miRNA from mass spectrometric data. The software includes capabilities such as miRNA search and mass calculator, modified miRNA mass calculator, and miRNA fragment search. MicroRNA MultiTool bridges the gap between experimental data and identification of miRNA by providing a rapid means of mass spectrometric data interpretation. Full article
(This article belongs to the Special Issue Bioinformatics Softwares and Databases for Non-Coding RNA Research)
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Open AccessArticle Tentative Characterization of Polyphenolic Compounds in the Male Flowers of Phoenix dactylifera by Liquid Chromatography Coupled with Mass Spectrometry and DFT
by , , , , , , and
Int. J. Mol. Sci. 2017, 18(3), 512; doi:10.3390/ijms18030512
Received: 28 December 2016 / Revised: 15 February 2017 / Accepted: 20 February 2017 / Published: 2 March 2017
Cited by 1 | Viewed by 445 | PDF Full-text (2354 KB) | HTML Full-text | XML Full-text
Abstract
Phoenix dacylifera is an ancient palm species rich in (poly)phenols. These phenolic compounds were tentatively identified by using liquid chromatography coupled with ion spray mass spectrometry in tandem mode (LC/MS/MS) with negative ion detection. Negative identification of the compounds was based on their
[...] Read more.
Phoenix dacylifera is an ancient palm species rich in (poly)phenols. These phenolic compounds were tentatively identified by using liquid chromatography coupled with ion spray mass spectrometry in tandem mode (LC/MS/MS) with negative ion detection. Negative identification of the compounds was based on their retention times and mass spectra in full scan mode (MS), and in different MS/MS modes. For the first time, complete hypothesis, and routs for both p-coumaroylshikimic acids (CoSA) and caffeoylshikimic acids (CSA) were suggested and confirmed by Density Fonctional Theory (DFT) study. Notably, of the 53 compounds characterized, 19 hydroxycinnamates derivatives were tentativelycharacterized in male flowers of date palm and 15 of them were recorded for the first time. In addition, five organic acids, six B-type proanthocyanidins, two anthocyanidin and 21 flavonoid derivatives have been tentatively characterized. Identification of B-type proanthocyanidins were based on the diagnostic ions resulting from heterocyclic ring fission (HRF) and retro-Diels-Alder (RDA) reaction of flavan-3-ol provided information on the hydroxylation pattern and the type of inter-flavan bond proanthocyanidins. The sequence of proanthocyanidins was detected through ions extracted from quinone methide (QM) cleavage of the inter-flavan bond. Full article
(This article belongs to the Special Issue Anthocyanins)
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Open AccessReview Mapping Post‐Transcriptional Modifications onto Transfer Ribonucleic Acid Sequences by Liquid Chromatography Tandem Mass Spectrometry
by , and
Biomolecules 2017, 7(1), 21; doi:10.3390/biom7010021
Received: 30 December 2016 / Accepted: 15 February 2017 / Published: 22 February 2017
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Abstract
Liquid chromatography, coupled with tandem mass spectrometry, has become one of the most popular methods for the analysis of post‐transcriptionally modified transfer ribonucleic acids (tRNAs). Given that the information collected using this platform is entirely determined by the mass of the analyte, it
[...] Read more.
Liquid chromatography, coupled with tandem mass spectrometry, has become one of the most popular methods for the analysis of post‐transcriptionally modified transfer ribonucleic acids (tRNAs). Given that the information collected using this platform is entirely determined by the mass of the analyte, it has proven to be the gold standard for accurately assigning nucleobases to the sequence. For the past few decades many labs have worked to improve the analysis, contiguous to instrumentation manufacturers developing faster and more sensitive instruments. With biological discoveries relating to ribonucleic acid happening more frequently, mass spectrometry has been invaluable in helping to understand what is happening at the molecular level. Here we present a brief overview of the methods that have been developed and refined for the analysis of modified tRNAs by liquid chromatography tandem mass spectrometry. Full article
(This article belongs to the Special Issue tRNA Modifications: Synthesis, Function and Beyond)
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Open AccessArticle QuEChERS Purification Combined with Ultrahigh-Performance Liquid Chromatography Tandem Mass Spectrometry for Simultaneous Quantification of 25 Mycotoxins in Cereals
by , , , , and
Toxins 2016, 8(12), 375; doi:10.3390/toxins8120375
Received: 4 May 2016 / Revised: 8 December 2016 / Accepted: 9 December 2016 / Published: 15 December 2016
Cited by 2 | Viewed by 450 | PDF Full-text (1706 KB) | HTML Full-text | XML Full-text
Abstract
A method based on the QuEChERS (quick, easy, cheap, effective, rugged, and safe) purification combined with ultrahigh performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS), was optimized for the simultaneous quantification of 25 mycotoxins in cereals. Samples were extracted with a solution containing 80%
[...] Read more.
A method based on the QuEChERS (quick, easy, cheap, effective, rugged, and safe) purification combined with ultrahigh performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS), was optimized for the simultaneous quantification of 25 mycotoxins in cereals. Samples were extracted with a solution containing 80% acetonitrile and 0.1% formic acid, and purified with QuEChERS before being separated by a C18 column. The mass spectrometry was conducted by using positive electrospray ionization (ESI+) and multiple reaction monitoring (MRM) models. The method gave good linear relations with regression coefficients ranging from 0.9950 to 0.9999. The detection limits ranged from 0.03 to 15.0 µg·kg−1, and the average recovery at three different concentrations ranged from 60.2% to 115.8%, with relative standard deviations (RSD%) varying from 0.7% to 19.6% for the 25 mycotoxins. The method is simple, rapid, accurate, and an improvement compared with the existing methods published so far. Full article
(This article belongs to the Special Issue LC-MS/MS Method for Mycotoxin Analysis)
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Open AccessArticle New Potential Biomarker for Methasterone Misuse in Human Urine by Liquid Chromatography Quadrupole Time of Flight Mass Spectrometry
by , , , , , and
Int. J. Mol. Sci. 2016, 17(10), 1628; doi:10.3390/ijms17101628
Received: 11 July 2016 / Revised: 14 September 2016 / Accepted: 19 September 2016 / Published: 24 September 2016
Viewed by 580 | PDF Full-text (2162 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, methasterone urinary metabolic profiles were investigated by liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) in full scan and targeted MS/MS modes with accurate mass measurement. A healthy male volunteer was asked to take the drug and liquid–liquid extraction
[...] Read more.
In this study, methasterone urinary metabolic profiles were investigated by liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) in full scan and targeted MS/MS modes with accurate mass measurement. A healthy male volunteer was asked to take the drug and liquid–liquid extraction was employed to process urine samples. Chromatographic peaks for potential metabolites were hunted out with the theoretical [M − H]− as a target ion in a full scan experiment and actual deprotonated ions were studied in targeted MS/MS experiment. Fifteen metabolites including two new sulfates (S1 and S2), three glucuronide conjugates (G2, G6 and G7), and three free metabolites (M2, M4 and M6) were detected for methasterone. Three metabolites involving G4, G5 and M5 were obtained for the first time in human urine samples. Owing to the absence of helpful fragments to elucidate the steroid ring structure of methasterone phase II metabolites, gas chromatography mass spectrometry (GC-MS) was employed to obtain structural information of the trimethylsilylated phase I metabolite released after enzymatic hydrolysis and the potential structure was inferred using a combined MS method. Metabolite detection times were also analyzed and G2 (18-nor-17β-hydroxymethyl-2α, 17α-dimethyl-androst-13-en-3α-ol-ξ-O-glucuronide) was thought to be new potential biomarker for methasterone misuse which can be detected up to 10 days. Full article
(This article belongs to the Special Issue Metabolomic Technologies in Medicine)
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Open AccessArticle Quantitative Detection of Trace Malachite Green in Aquiculture Water Samples by Extractive Electrospray Ionization Mass Spectrometry
by , , , , , and
Int. J. Environ. Res. Public Health 2016, 13(8), 814; doi:10.3390/ijerph13080814
Received: 8 May 2016 / Revised: 24 July 2016 / Accepted: 5 August 2016 / Published: 11 August 2016
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Abstract
Exposure to malachite green (MG) may pose great health risks to humans; thus, it is of prime importance to develop fast and robust methods to quantitatively screen the presence of malachite green in water. Herein the application of extractive electrospray ionization mass spectrometry
[...] Read more.
Exposure to malachite green (MG) may pose great health risks to humans; thus, it is of prime importance to develop fast and robust methods to quantitatively screen the presence of malachite green in water. Herein the application of extractive electrospray ionization mass spectrometry (EESI-MS) has been extended to the trace detection of MG within lake water and aquiculture water, due to the intensive use of MG as a biocide in fisheries. This method has the advantage of obviating offline liquid-liquid extraction or tedious matrix separation prior to the measurement of malachite green in native aqueous medium. The experimental results indicate that the extrapolated detection limit for MG was ~3.8 μg·L−1 (S/N = 3) in lake water samples and ~0.5 μg·L−1 in ultrapure water under optimized experimental conditions. The signal intensity of MG showed good linearity over the concentration range of 10–1000 μg·L−1. Measurement of practical water samples fortified with MG at 0.01, 0.1 and 1.0 mg·L−1 gave a good validation of the established calibration curve. The average recoveries and relative standard deviation (RSD) of malachite green in lake water and Carassius carassius fish farm effluent water were 115% (6.64% RSD), 85.4% (9.17% RSD) and 96.0% (7.44% RSD), respectively. Overall, the established EESI-MS/MS method has been demonstrated suitable for sensitive and rapid (<2 min per sample) quantitative detection of malachite green in various aqueous media, indicating its potential for online real-time monitoring of real life samples. Full article
(This article belongs to the Special Issue Emerging Aquatic Microbial and Chemical Contaminants of Concern and Their Impact on Human Health)
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Open AccessArticle Fourier Transform Mass Spectrometry and Nuclear Magnetic Resonance Analysis for the Rapid and Accurate Characterization of Hexacosanoylceramide
by , , , , and
Int. J. Mol. Sci. 2016, 17(7), 1024; doi:10.3390/ijms17071024
Received: 29 February 2016 / Revised: 3 May 2016 / Accepted: 16 May 2016 / Published: 28 June 2016
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Abstract
Ceramides are a central unit of all sphingolipids which have been identified as sites of biological recognition on cellular membranes mediating cell growth and differentiation. Several glycosphingolipids have been isolated, displaying immunomodulatory and anti-tumor activities. These molecules have generated considerable interest as potential
[...] Read more.
Ceramides are a central unit of all sphingolipids which have been identified as sites of biological recognition on cellular membranes mediating cell growth and differentiation. Several glycosphingolipids have been isolated, displaying immunomodulatory and anti-tumor activities. These molecules have generated considerable interest as potential vaccine adjuvants in humans. Accurate analyses of these and related sphingosine analogues are important for the characterization of structure, biological function, and metabolism. We report the complementary use of direct laser desorption ionization (DLDI), sheath flow electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and high-field nuclear magnetic resonance (NMR) analysis for the rapid, accurate identification of hexacosanoylceramide and starting materials. DLDI does not require stringent sample preparation and yields representative ions. Sheath-flow ESI yields ions of the product and byproducts and was significantly better than monospray ESI due to improved compound solubility. Negative ion sheath flow ESI provided data of starting materials and products all in one acquisition as hexacosanoic acid does not ionize efficiently when ceramides are present. NMR provided characterization of these lipid molecules complementing the results obtained from MS analyses. NMR data was able to differentiate straight chain versus branched chain alkyl groups not easily obtained from mass spectrometry. Full article
(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)
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Open AccessReview Applications of Fourier Transform Ion Cyclotron Resonance (FT-ICR) and Orbitrap Based High Resolution Mass Spectrometry in Metabolomics and Lipidomics
by , and
Int. J. Mol. Sci. 2016, 17(6), 816; doi:10.3390/ijms17060816
Received: 1 April 2016 / Revised: 14 May 2016 / Accepted: 17 May 2016 / Published: 25 May 2016
Cited by 9 | Viewed by 1175 | PDF Full-text (945 KB) | HTML Full-text | XML Full-text
Abstract
Metabolomics, along with other “omics” approaches, is rapidly becoming one of the major approaches aimed at understanding the organization and dynamics of metabolic networks. Mass spectrometry is often a technique of choice for metabolomics studies due to its high sensitivity, reproducibility and wide
[...] Read more.
Metabolomics, along with other “omics” approaches, is rapidly becoming one of the major approaches aimed at understanding the organization and dynamics of metabolic networks. Mass spectrometry is often a technique of choice for metabolomics studies due to its high sensitivity, reproducibility and wide dynamic range. High resolution mass spectrometry (HRMS) is a widely practiced technique in analytical and bioanalytical sciences. It offers exceptionally high resolution and the highest degree of structural confirmation. Many metabolomics studies have been conducted using HRMS over the past decade. In this review, we will explore the latest developments in Fourier transform mass spectrometry (FTMS) and Orbitrap based metabolomics technology, its advantages and drawbacks for using in metabolomics and lipidomics studies, and development of novel approaches for processing HRMS data. Full article
(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)
Open AccessCommunication Comprehensive Qualitative Ingredient Profiling of Chinese Herbal Formula Wu-Zhu-Yu Decoction via a Mass Defect and Fragment Filtering Approach Using High Resolution Mass Spectrometry
by , , , , and
Molecules 2016, 21(5), 664; doi:10.3390/molecules21050664
Received: 12 April 2016 / Revised: 10 May 2016 / Accepted: 16 May 2016 / Published: 19 May 2016
Cited by 3 | Viewed by 755 | PDF Full-text (2066 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The Wu-Zhu-Yu decoction is a traditional Chinese medicine formula for the treatment of headache. To reveal its material basis, a rapid and reliable liquid chromatography-high resolution mass spectrometry method was established for comprehensive profiling of the chemical ingredients in the Wu-Zhu-Yu decoction. The
[...] Read more.
The Wu-Zhu-Yu decoction is a traditional Chinese medicine formula for the treatment of headache. To reveal its material basis, a rapid and reliable liquid chromatography-high resolution mass spectrometry method was established for comprehensive profiling of the chemical ingredients in the Wu-Zhu-Yu decoction. The method was used on a quadrupole time-of-flight mass spectrometer along with an advanced data processing procedure consisting of mass accuracy screening, mass defect filtering and fragment filtering. After eliminating interference with a filtering approach, the MS data profiling was made more distinct and accurate. With the optimized conditions of only 35 min LC separation and single sample injection of each positive or negative ion mode, a total of 168 compounds were characterized, including 23 evodiamine and its analogous alkaloids, 12 limonoids, 17 gingerols, 38 ginsenosides, 15 flavonoids, 16 organic acids, 14 alkaloids, 5 saponins, 3 2,2-dimethylchromenes and 25 other compounds. The fragmentation patterns of representative compounds were illustrated as well. Integrative qualitative analysis of the Wu-Zhu-Yu decoction by high resolution mass spectrometry was accomplished and reported for the first time. The study demonstrated that the established method was a powerful and reliable strategy for comprehensive detection and would be widely applicable for identification of complicated components from herbal prescriptions, and may provide a basis for chemical analysis of other complex mixtures. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A Simple Method for the Evaluation of the Pulse Width of an Ultraviolet Femtosecond Laser Used in Two-Photon Ionization Mass Spectrometry
by , , and
Appl. Sci. 2016, 6(5), 136; doi:10.3390/app6050136
Received: 21 March 2016 / Accepted: 29 April 2016 / Published: 6 May 2016
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Abstract
A simple method was proposed for on-site evaluation of the pulse width of an ultraviolet femtosecond laser coupled with a mass spectrometer. This technique was based on measurement of a two-photon ionization signal in mass spectrometry by translation of the prism in the
[...] Read more.
A simple method was proposed for on-site evaluation of the pulse width of an ultraviolet femtosecond laser coupled with a mass spectrometer. This technique was based on measurement of a two-photon ionization signal in mass spectrometry by translation of the prism in the pulse compressor of the femtosecond laser. The method was applied to optical pulses that were emitted at wavelengths of 267, 241, and 219 nm; the latter two pulses were generated by four-wave Raman mixing using the third harmonic emission of a Ti:sapphire laser (267 nm) in hydrogen gas. The measurement results show that this approach is useful for evaluation of the pulse width of the ultraviolet femtosecond laser used in mass spectrometry for trace analysis of organic compounds. Full article
(This article belongs to the Special Issue Multi-Color Laser Emission for the Generation of Ultrashort Optical Pulse) Printed Edition available
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Open AccessArticle The Role of Ultrahigh Resolution Fourier Transform Mass Spectrometry (FT-MS) in Astrobiology-Related Research: Analysis of Meteorites and Tholins
by , , and
Int. J. Mol. Sci. 2016, 17(4), 439; doi:10.3390/ijms17040439
Received: 9 November 2015 / Revised: 9 March 2016 / Accepted: 9 March 2016 / Published: 24 March 2016
Cited by 1 | Viewed by 751 | PDF Full-text (1253 KB) | HTML Full-text | XML Full-text
Abstract
It is an important but also a challenging analytical problem to understand the chemical composition and structure of prebiotic organic matter that is present in extraterrestrial materials. Its formation, evolution and content in the building blocks (“seeds”) for more complex molecules, such as
[...] Read more.
It is an important but also a challenging analytical problem to understand the chemical composition and structure of prebiotic organic matter that is present in extraterrestrial materials. Its formation, evolution and content in the building blocks (“seeds”) for more complex molecules, such as proteins and DNA, are key questions in the field of exobiology. Ultrahigh resolution mass spectrometry is one of the best analytical techniques that can be applied because it provides reliable information on the chemical composition and structure of individual components of complex organic mixtures. Prebiotic organic material is delivered to Earth by meteorites or generated in laboratories in simulation (model) experiments that mimic space or atmospheric conditions. Recent representative examples for ultrahigh resolution mass spectrometry studies using Fourier-transform (FT) mass spectrometers such as Orbitrap and ion cyclotron resonance (ICR) mass spectrometers are shown and discussed in the present article, including: (i) the analysis of organic matter of meteorites; (ii) modeling atmospheric processes in ICR cells; and (iii) the structural analysis of laboratory made tholins that might be present in the atmosphere and surface of Saturn’s largest moon, Titan. Full article
(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)
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Open AccessReview Bioprospecting of Marine Macrophytes Using MS-Based Lipidomics as a New Approach
by , , , , and
Mar. Drugs 2016, 14(3), 49; doi:10.3390/md14030049
Received: 21 December 2015 / Revised: 25 February 2016 / Accepted: 2 March 2016 / Published: 8 March 2016
Cited by 2 | Viewed by 1257 | PDF Full-text (1955 KB) | HTML Full-text | XML Full-text
Abstract
The marine environment supports a remarkable diversity of organisms which are a potential source of natural products with biological activities. These organisms include a wide variety of marine plants (from micro- to macrophytes), which have been used in the food and pharmaceutical industry.
[...] Read more.
The marine environment supports a remarkable diversity of organisms which are a potential source of natural products with biological activities. These organisms include a wide variety of marine plants (from micro- to macrophytes), which have been used in the food and pharmaceutical industry. However, the biochemistry and biological activities of many of these macrophytes (namely macroalgae and halophytes, including seagrasses) are still far from being fully explored. Most popular bioactive components include polysaccharides, peptides, phenolics and fatty acids (FAs). Polar lipids (glycolipids, phospholipids and betaine lipids) are emerging as novel value-added bioactive phytochemicals, rich in n-3 FA, with high nutritional value and health beneficial effects for the prevention of chronic diseases. Polar lipids account various combinations of polar groups, fatty acyl chains and backbone structures. The polar lipidome of macrophytes is remarkably diverse, and its screening represents a significant analytical challenge. Modern research platforms, particularly mass spectrometry (MS)-based lipidomic approaches, have been recently used to address this challenge and are here reviewed. The application of lipidomics to address lipid composition of marine macrophytes will contribute to the stimulation of further research on this group and foster the exploration of novel applications. Full article
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Open AccessReview Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS): A New Tool for the Analysis of Toxicological Effects on Single Cell Level
by , and
Toxics 2016, 4(1), 5; doi:10.3390/toxics4010005
Received: 22 December 2015 / Revised: 2 February 2016 / Accepted: 6 February 2016 / Published: 15 February 2016
Cited by 1 | Viewed by 995 | PDF Full-text (990 KB) | HTML Full-text | XML Full-text
Abstract
Single cell imaging mass spectrometry opens up a complete new perspective for strategies in toxicological risk assessment and drug discovery. In particular, time-of-flight secondary ion mass spectrometry (ToF-SIMS) with its high spatial and depth resolution is becoming part of the imaging mass spectrometry
[...] Read more.
Single cell imaging mass spectrometry opens up a complete new perspective for strategies in toxicological risk assessment and drug discovery. In particular, time-of-flight secondary ion mass spectrometry (ToF-SIMS) with its high spatial and depth resolution is becoming part of the imaging mass spectrometry toolbox used for single cell analysis. Recent instrumentation advancements in combination with newly developed cluster ion guns allow 3-dimensional reconstruction of single cells together with a spatially resolved compound location and quantification on nanoscale depth level. The exact location and quantification of a single compound or even of a set of compounds is no longer restricted to the two dimensional space within single cells, but is available for voxels, a cube-sized 3-dimensional space, rather than pixels. The information gathered from one voxel is further analysed using multivariate statistical methodology like maximum autocorrelation factors to co-locate the compounds of interest within intracellular organelles like nucleus, mitochondria or golgi apparatus. Furthermore, the cell membrane may be resolved, including adhering compounds and potential changes of the lipid patterns. The generated information can be used further for a first evaluation of intracellular target specifity of new drug candidates or for the toxicological risk assessment of environmental chemicals and their intracellular metabolites. Additionally, single cell lipidomics and metabolomics enable for the first time an in-depth understanding of the activation or inhibition of cellular biosynthesis and signalling pathways. Full article
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Open AccessArticle Direct Analysis in Real Time (DART) of an Organothiophosphate at Ultrahigh Resolution by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry
by and
Int. J. Mol. Sci. 2016, 17(1), 116; doi:10.3390/ijms17010116
Received: 29 November 2015 / Revised: 23 December 2015 / Accepted: 8 January 2016 / Published: 16 January 2016
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Abstract
Direct analysis in real time (DART) is a recently developed ambient ionization technique for mass spectrometry to enable rapid and sensitive analyses with little or no sample preparation. After swab-based field sampling, the organothiophosphate malathion was analyzed using DART-Fourier transform ion cyclotron resonance
[...] Read more.
Direct analysis in real time (DART) is a recently developed ambient ionization technique for mass spectrometry to enable rapid and sensitive analyses with little or no sample preparation. After swab-based field sampling, the organothiophosphate malathion was analyzed using DART-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Mass resolution was documented to be over 800,000 in full-scan MS mode and over 1,000,000 for an MS/MS product ion produced by collision-induced dissociation of the protonated analyte. Mass measurement accuracy below 1 ppm was obtained for all DART-generated ions that belonged to the test compound in the mass spectra acquired using only external mass calibration. This high mass measurement accuracy, achievable at present only through FTMS, was required for unequivocal identification of the corresponding molecular formulae. Full article
(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)
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Open AccessReview Fourier Transform Mass Spectrometry: The Transformation of Modern Environmental Analyses
by , , , and
Int. J. Mol. Sci. 2016, 17(1), 104; doi:10.3390/ijms17010104
Received: 30 October 2015 / Revised: 21 December 2015 / Accepted: 28 December 2015 / Published: 14 January 2016
Cited by 1 | Viewed by 896 | PDF Full-text (768 KB) | HTML Full-text | XML Full-text
Abstract
Unknown compounds in environmental samples are difficult to identify using standard mass spectrometric methods. Fourier transform mass spectrometry (FTMS) has revolutionized how environmental analyses are performed. With its unsurpassed mass accuracy, high resolution and sensitivity, researchers now have a tool for difficult and
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Unknown compounds in environmental samples are difficult to identify using standard mass spectrometric methods. Fourier transform mass spectrometry (FTMS) has revolutionized how environmental analyses are performed. With its unsurpassed mass accuracy, high resolution and sensitivity, researchers now have a tool for difficult and complex environmental analyses. Two features of FTMS are responsible for changing the face of how complex analyses are accomplished. First is the ability to quickly and with high mass accuracy determine the presence of unknown chemical residues in samples. For years, the field has been limited by mass spectrometric methods that were based on knowing what compounds of interest were. Secondly, by utilizing the high resolution capabilities coupled with the low detection limits of FTMS, analysts also could dilute the sample sufficiently to minimize the ionization changes from varied matrices. Full article
(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)
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Open AccessArticle Selective Analysis of Sulfur-Containing Species in a Heavy Crude Oil by Deuterium Labeling Reactions and Ultrahigh Resolution Mass Spectrometry
by and
Int. J. Mol. Sci. 2015, 16(12), 30133-30143; doi:10.3390/ijms161226205
Received: 3 November 2015 / Revised: 4 December 2015 / Accepted: 9 December 2015 / Published: 17 December 2015
Cited by 2 | Viewed by 923 | PDF Full-text (3738 KB) | HTML Full-text | XML Full-text
Abstract
A heavy crude oil has been treated with deuterated alkylating reagents (CD3I and C2D5I) and directly analyzed without any prior fractionation and chromatographic separation by high-field Orbitrap Fourier Transform Mass Spectrometry (FTMS) and Fourier Transform Ion Cyclotron
[...] Read more.
A heavy crude oil has been treated with deuterated alkylating reagents (CD3I and C2D5I) and directly analyzed without any prior fractionation and chromatographic separation by high-field Orbitrap Fourier Transform Mass Spectrometry (FTMS) and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) using electrospray ionization (ESI). The reaction of a polycyclic aromatic sulfur heterocycles (PASHs) dibenzothiophene (DBT), in the presence of silver tetrafluoroborate (AgBF4) with ethyl iodide (C2H5I) in anhydrous dichloroethane (DCE) was optimized as a sample reaction to study heavy crude oil mixtures, and the reaction yield was monitored and determined by proton nuclear magnetic resonance spectroscopy (1H-NMR). The obtained conditions were then applied to a mixture of standard aromatic CH-, N-, O- and S-containing compounds and then a heavy crude oil, and only sulfur-containing compounds were selectively alkylated. The deuterium labeled alkylating reagents, iodomethane-d3 (CD3I) and iodoethane-d5 (C2D5I), were employed to the alkylation of heavy crude oil to selectively differentiate the tagged sulfur species from the original crude oil. Full article
(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)
Open AccessArticle Recommended Mass Spectrometry-Based Strategies to Identify Ricin-Containing Samples
by , , , , and
Toxins 2015, 7(12), 4881-4894; doi:10.3390/toxins7124854
Received: 25 June 2015 / Revised: 4 August 2015 / Accepted: 24 August 2015 / Published: 25 November 2015
Cited by 3 | Viewed by 1005 | PDF Full-text (877 KB) | HTML Full-text | XML Full-text
Abstract
Ricin is a protein toxin produced by the castor bean plant (Ricinus communis) together with a related protein known as R. communis agglutinin (RCA120). Mass spectrometric (MS) assays have the capacity to unambiguously identify ricin and to detect ricin’s activity in
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Ricin is a protein toxin produced by the castor bean plant (Ricinus communis) together with a related protein known as R. communis agglutinin (RCA120). Mass spectrometric (MS) assays have the capacity to unambiguously identify ricin and to detect ricin’s activity in samples with complex matrices. These qualitative and quantitative assays enable detection and differentiation of ricin from the less toxic RCA120 through determination of the amino acid sequence of the protein in question, and active ricin can be monitored by MS as the release of adenine from the depurination of a nucleic acid substrate. In this work, we describe the application of MS-based methods to detect, differentiate and quantify ricin and RCA120 in nine blinded samples supplied as part of the EQuATox proficiency test. Overall, MS-based assays successfully identified all samples containing ricin or RCA120 with the exception of the sample spiked with the lowest concentration (0.414 ng/mL). In fact, mass spectrometry was the most successful method for differentiation of ricin and RCA120 based on amino acid determination. Mass spectrometric methods were also successful at ranking the functional activities of the samples, successfully yielding semi-quantitative results. These results indicate that MS-based assays are excellent techniques to detect, differentiate, and quantify ricin and RCA120 in complex matrices. Full article
(This article belongs to the Special Issue Detection and identification of biological toxins in international proficiency tests)
Open AccessArticle Two-Dimensional N-Glycan Distribution Mapping of Hepatocellular Carcinoma Tissues by MALDI-Imaging Mass Spectrometry
by , , , and
Biomolecules 2015, 5(4), 2554-2572; doi:10.3390/biom5042554
Received: 16 June 2015 / Revised: 18 September 2015 / Accepted: 28 September 2015 / Published: 15 October 2015
Cited by 9 | Viewed by 1544 | PDF Full-text (2315 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new mass spectrometry imaging approach to simultaneously map the two-dimensional distribution of N-glycans in tissues has been recently developed. The method uses Matrix Assisted Laser Desorption Ionization Imaging Mass Spectrometry (MALDI-IMS) to spatially profile the location and distribution of multiple N
[...] Read more.
A new mass spectrometry imaging approach to simultaneously map the two-dimensional distribution of N-glycans in tissues has been recently developed. The method uses Matrix Assisted Laser Desorption Ionization Imaging Mass Spectrometry (MALDI-IMS) to spatially profile the location and distribution of multiple N-linked glycan species released by peptide N-glycosidase F in frozen or formalin-fixed tissues. Multiple formalin-fixed human hepatocellular carcinoma tissues were evaluated with this method, resulting in a panel of over 30 N-glycans detected. An ethylation reaction of extracted N-glycans released from adjacent slides was done to stabilize sialic acid containing glycans, and these structures were compared to N-glycans detected directly from tissue profiling. In addition, the distribution of singly fucosylated N-glycans detected in tumor tissue microarray cores were compared to the histochemistry staining pattern of a core fucose binding lectin. As this MALDI-IMS workflow has the potential to be applied to any formalin-fixed tissue block or tissue microarray, the advantages and limitations of the technique in context with other glycomic methods are also summarized. Full article
(This article belongs to the Special Issue Challenges in Glycan, Glycoprotein and Proteoglycan Research)
Open AccessReview May the Best Molecule Win: Competition ESI Mass Spectrometry
by and
Int. J. Mol. Sci. 2015, 16(10), 24506-24531; doi:10.3390/ijms161024506
Received: 28 August 2015 / Revised: 18 September 2015 / Accepted: 9 October 2015 / Published: 15 October 2015
Cited by 2 | Viewed by 1149 | PDF Full-text (2878 KB) | HTML Full-text | XML Full-text
Abstract
Electrospray ionization mass spectrometry has become invaluable in the characterization of macromolecular biological systems such as nucleic acids and proteins. Recent advances in the field of mass spectrometry and the soft conditions characteristic of electrospray ionization allow for the investigation of non-covalent interactions
[...] Read more.
Electrospray ionization mass spectrometry has become invaluable in the characterization of macromolecular biological systems such as nucleic acids and proteins. Recent advances in the field of mass spectrometry and the soft conditions characteristic of electrospray ionization allow for the investigation of non-covalent interactions among large biomolecules and ligands. Modulation of genetic processes through the use of small molecule inhibitors with the DNA minor groove is gaining attention as a potential therapeutic approach. In this review, we discuss the development of a competition method using electrospray ionization mass spectrometry to probe the interactions of multiple DNA sequences with libraries of minor groove binding molecules. Such an approach acts as a high-throughput screening method to determine important information including the stoichiometry, binding mode, cooperativity, and relative binding affinity. In addition to small molecule-DNA complexes, we highlight other applications in which competition mass spectrometry has been used. A competitive approach to simultaneously investigate complex interactions promises to be a powerful tool in the discovery of small molecule inhibitors with high specificity and for specific, important DNA sequences. Full article
(This article belongs to the Special Issue Low Molecular Weight DNA and RNA Binding Agents)
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Open AccessArticle Qualitative and Quantitative Analysis of Major Triterpenoids in Alismatis Rhizoma by High Performance Liquid Chromatography/Diode-Array Detector/Quadrupole-Time-of-Flight Mass Spectrometry and Ultra-Performance Liquid Chromatography/Triple Quadrupole Mass Spectrometry
by , , , , , , , and
Molecules 2015, 20(8), 13958-13981; doi:10.3390/molecules200813958
Received: 30 June 2015 / Revised: 26 July 2015 / Accepted: 28 July 2015 / Published: 31 July 2015
Cited by 3 | Viewed by 1650 | PDF Full-text (2406 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Alismatis Rhizoma (AMR) is a well-known natural medicine with a long history in Chinese medicine and has been commonly used for treating a wide range of ailments related to dysuria, edema, nephropathy, hyperlipidaemia, diabetes, inflammation as well as tumors in clinical applications. Most
[...] Read more.
Alismatis Rhizoma (AMR) is a well-known natural medicine with a long history in Chinese medicine and has been commonly used for treating a wide range of ailments related to dysuria, edema, nephropathy, hyperlipidaemia, diabetes, inflammation as well as tumors in clinical applications. Most beneficial effects of AMR are attributed to the presence of protostane terpenoids, the major active ingredients of Alismatis Rhizoma (AMR). In this study, a systematic high performance liquid chromatography/diode-array detector/quadrupole-time-of-flight mass spectrometry (HPLC-DAD-Q-TOF MS) and ultra-performance liquid chromatography/triple quadrupole mass spectrometry (UPLC-QqQ MS) method was developed for qualitative and quantitative analyses of the major AMR triterpenoids. First, a total of 25 triterpenoid components, including 24 known compounds and one new compound were identified by comparison with UV spectra, molecular ions and fragmentation behaviors of reference standards or the literature. Second, an efficient method was established for the rapid simultaneous determination of 14 representative triterpenoids by UPLC-QqQ MS. Forty-three batches of AMR were analyzed with linearity (r, 0.9980–0.9999), intra-day precision (RSD, 1.18%–3.79%), inter-day precision (RSD, 1.53%–3.96%), stability (RSD, 1.32%–3.97%), repeatability (RSD, 2.21%–4.25%), and recovery (98.11%–103.8%). These results indicated that new approaches combining HPLC-DAD-Q-TOF MS and UPLC-QqQ MS are applicable in the qualitative and quantitative analysis of AMR. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Mass Spectrometry-Based Proteomics for Pre-Eclampsia and Preterm Birth
by , , and
Int. J. Mol. Sci. 2015, 16(5), 10952-10985; doi:10.3390/ijms160510952
Received: 31 March 2015 / Accepted: 4 May 2015 / Published: 14 May 2015
Cited by 8 | Viewed by 1926 | PDF Full-text (1954 KB) | HTML Full-text | XML Full-text
Abstract
Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic
[...] Read more.
Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic prematurity. Fifteen million infants are born preterm each year globally, but more than one million of those do not survive their first month of life. Currently there are no predictive tests available for diagnosis of these pregnancy-related complications and the biological mechanisms of the diseases have not been fully elucidated. Mass spectrometry-based proteomics have all the necessary attributes to provide the needed breakthrough in understanding the pathophysiology of complex human diseases thorough the discovery of biomarkers. The mass spectrometry methodologies employed in the studies for pregnancy-related complications are evaluated in this article. Top-down proteomic and peptidomic profiling by laser mass spectrometry, liquid chromatography or capillary electrophoresis coupled to mass spectrometry, and bottom-up quantitative proteomics and targeted proteomics by liquid chromatography mass spectrometry have been applied to elucidate protein biomarkers and biological mechanism of pregnancy-related complications. The proteomes of serum, urine, amniotic fluid, cervical-vaginal fluid, placental tissue, and cytotrophoblastic cells have all been investigated. Numerous biomarkers or biomarker candidates that could distinguish complicated pregnancies from healthy controls have been proposed. Nevertheless, questions as to the clinically utility and the capacity to elucidate the pathogenesis of the pre-eclampsia and preterm birth remain to be answered. Full article
(This article belongs to the Special Issue Prediction, Diagnostics and Prevention of Pregnancy Complications)
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Open AccessArticle Determination of Oxidized Phosphatidylcholines by Hydrophilic Interaction Liquid Chromatography Coupled to Fourier Transform Mass Spectrometry
by , , , , , , , and
Int. J. Mol. Sci. 2015, 16(4), 8351-8363; doi:10.3390/ijms16048351
Received: 5 March 2015 / Revised: 2 April 2015 / Accepted: 8 April 2015 / Published: 14 April 2015
Cited by 3 | Viewed by 1243 | PDF Full-text (720 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel liquid chromatography-mass spectrometry (LC-MS) approach for analysis of oxidized phosphatidylcholines by an Orbitrap Fourier Transform mass spectrometer in positive electrospray ionization (ESI) coupled to hydrophilic interaction liquid chromatography (HILIC) was developed. This method depends on three selectivity criteria for separation and
[...] Read more.
A novel liquid chromatography-mass spectrometry (LC-MS) approach for analysis of oxidized phosphatidylcholines by an Orbitrap Fourier Transform mass spectrometer in positive electrospray ionization (ESI) coupled to hydrophilic interaction liquid chromatography (HILIC) was developed. This method depends on three selectivity criteria for separation and identification: retention time, exact mass at a resolution of 100,000 and collision induced dissociation (CID) fragment spectra in a linear ion trap. The process of chromatography development showed the best separation properties with a silica-based Kinetex column. This type of chromatography was able to separate all major lipid classes expected in mammalian samples, yielding increased sensitivity of oxidized phosphatidylcholines over reversed phase chromatography. Identification of molecular species was achieved by exact mass on intact molecular ions and CID tandem mass spectra containing characteristic fragments. Due to a lack of commercially available standards, method development was performed with copper induced oxidation products of palmitoyl-arachidonoyl-phosphatidylcholine, which resulted in a plethora of lipid species oxidized at the arachidonoyl moiety. Validation of the method was done with copper oxidized human low-density lipoprotein (LDL) prepared by ultracentrifugation. In these LDL samples we could identify 46 oxidized molecular phosphatidylcholine species out of 99 possible candidates. Full article
(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)
Open AccessArticle Analyses of Phytohormones in Coconut (Cocos Nucifera L.) Water Using Capillary Electrophoresis-Tandem Mass Spectrometry
by , and
Chromatography 2014, 1(4), 211-226; doi:10.3390/chromatography1040211
Received: 8 October 2014 / Revised: 8 December 2014 / Accepted: 12 December 2014 / Published: 22 December 2014
Cited by 2 | Viewed by 1748 | PDF Full-text (1228 KB) | HTML Full-text | XML Full-text
Abstract
Capillary electrophoresis (CE) coupled with mass spectrometry (MS) or tandem mass spectrometry (MS/MS) is reported as an alternative and potentially useful method for the simultaneous analysis of various classes of phytohormones with diversified structures, including indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), abscisic acid
[...] Read more.
Capillary electrophoresis (CE) coupled with mass spectrometry (MS) or tandem mass spectrometry (MS/MS) is reported as an alternative and potentially useful method for the simultaneous analysis of various classes of phytohormones with diversified structures, including indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), abscisic acid (ABA), gibberellic acid (GA), zeatin (Z), N6-benzyladenine (BA), α-naphthaleneacetic acid (NAA) and 2,4-dichlorophenoxyacetic acid (2,4-D). The key to the CE-MS/MS analysis was based on electroosmotic flow reversal using a cationic polymer-coated capillary. Under optimum conditions, a baseline separation of eight phytohormones was accomplished within 30 min using 60 mM ammonium formate/formic acid buffer of pH 3.8 with −20 kV as the separation voltage. The accessibility of MS/MS together with the characterization by migration properties obtained by CE allows for the development of CE-MS/MS as an emerging potential method for the analysis of different classes of phytohormones in a single run. The utility of the CE-MS/MS method was demonstrated by the comprehensive screening of phytohormones in coconut (Cocos nucifera L.) water after pre-concentration and purification through solid-phase extraction (SPE) cartridge. IAA, ABA, GA and Z were detected and quantified in the purified coconut water extract sample. Full article
(This article belongs to the Special Issue Advances in Hyphenated Methods in Separation)
Open AccessArticle Investigation of Dendriplexes by Ion Mobility-Mass Spectrometry
by , , , , , and
Molecules 2014, 19(12), 20731-20750; doi:10.3390/molecules191220731
Received: 24 July 2014 / Revised: 22 October 2014 / Accepted: 27 October 2014 / Published: 12 December 2014
Cited by 1 | Viewed by 1417 | PDF Full-text (3141 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Highly branched polyamidoamine (PAMAM) dendrimers presenting biological activities have been envisaged as non-viral gene delivery vectors. They are known to associate with nucleic acid (DNA) in non-covalent complexes via electrostatic interactions. Although their transfection efficiency has been proved, PAMAMs present a significant cytotoxicity
[...] Read more.
Highly branched polyamidoamine (PAMAM) dendrimers presenting biological activities have been envisaged as non-viral gene delivery vectors. They are known to associate with nucleic acid (DNA) in non-covalent complexes via electrostatic interactions. Although their transfection efficiency has been proved, PAMAMs present a significant cytotoxicity due to their cationic surface. To overcome such a drawback, different chemical modifications of the PAMAM surface have been reported such as the attachment of hydrophobic residues. In the present work, we studied the complexation of DNA duplexes with different low-generation PAMAM; ammonia-cored G0(N) and G1(N) PAMAM, native or chemically modified with aromatic residues, i.e., phenyl-modified-PAMAM G0(N) and phenylalanine-modified-PAMAM G1(N). To investigate the interactions involved in the PAMAM/DNA complexes, also called dendriplexes, we used electrospray ionization (ESI) coupled to ion mobility spectrometry-mass-spectrometry (IM-MS). ESI is known to allow the study of non-covalent complexes in native conditions while IM-MS is a bidimensional separation technique particularly useful for the characterization of complex mixtures. IM-MS allows the separation of the expected complexes, possible additional non-specific complexes and the free ligands. Tandem mass spectrometry (MS/MS) was also used for the structural characterization. This work highlights the contribution of IM-MS and MS/MS for the study of small dendriplexes. The stoichiometries of the complexes and the equilibrium dissociation constants were determined. The [DNA/native PAMAM] and [DNA/modified-PAMAM] dendriplexes were compared. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
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Open AccessArticle MALDI Mass Spectrometry Imaging for the Simultaneous Location of Resveratrol, Pterostilbene and Viniferins on Grapevine Leaves
by , , , and
Molecules 2014, 19(7), 10587-10600; doi:10.3390/molecules190710587
Received: 4 May 2014 / Revised: 1 July 2014 / Accepted: 16 July 2014 / Published: 21 July 2014
Cited by 12 | Viewed by 2439 | PDF Full-text (739 KB) | HTML Full-text | XML Full-text
Abstract
To investigate the in-situ response to a stress, grapevine leaves have been subjected to mass spectrometry imaging (MSI) experiments. The Matrix Assisted Laser Desorption/Ionisation (MALDI) approach using different matrices has been evaluated. Among all the tested matrices, the 2,5-dihydroxybenzoic acid (DHB) was found
[...] Read more.
To investigate the in-situ response to a stress, grapevine leaves have been subjected to mass spectrometry imaging (MSI) experiments. The Matrix Assisted Laser Desorption/Ionisation (MALDI) approach using different matrices has been evaluated. Among all the tested matrices, the 2,5-dihydroxybenzoic acid (DHB) was found to be the most efficient matrix allowing a broader range of detected stilbene phytoalexins. Resveratrol, but also more toxic compounds against fungi such as pterostilbene and viniferins, were identified and mapped. Their spatial distributions on grapevine leaves irradiated by UV show their specific colocation around the veins. Moreover, MALDI MSI reveals that resveratrol (and piceids) and viniferins are not specifically located on the same area when leaves are infected by Plasmopara viticola. Results obtained by MALDI mass spectrometry imaging demonstrate that this technique would be essential to improve the level of knowledge concerning the role of the stilbene phytoalexins involved in a stress event. Full article
(This article belongs to the Special Issue Phytoalexins: Current Progress and Future Prospects) Printed Edition available
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Open AccessArticle Confirmation of Pinnatoxins and Spirolides in Shellfish and Passive Samplers from Catalonia (Spain) by Liquid Chromatography Coupled with Triple Quadrupole and High-Resolution Hybrid Tandem Mass Spectrometry
by , , , , and
Mar. Drugs 2014, 12(6), 3706-3732; doi:10.3390/md12063706
Received: 4 April 2014 / Revised: 13 May 2014 / Accepted: 19 May 2014 / Published: 23 June 2014
Cited by 13 | Viewed by 1666 | PDF Full-text (1011 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cyclic imines are lipophilic marine toxins that bioaccumulate in seafood. Their structure comprises a cyclic-imino moiety, responsible for acute neurotoxicity in mice. Cyclic imines have not been linked yet to human poisonings and are not regulated in Europe, although the European Food Safety
[...] Read more.
Cyclic imines are lipophilic marine toxins that bioaccumulate in seafood. Their structure comprises a cyclic-imino moiety, responsible for acute neurotoxicity in mice. Cyclic imines have not been linked yet to human poisonings and are not regulated in Europe, although the European Food Safety Authority requires more data to perform a conclusive risk assessment for consumers. This work presents the first detection of pinnatoxin G (PnTX-G) in Spain and 13-desmethyl spirolide C (SPX-1) in shellfish from Catalonia (Spain, NW Mediterranean Sea). Cyclic imines were found at low concentrations (2 to 60 µg/kg) in 13 samples of mussels and oysters (22 samples analyzed). Pinnatoxin G has been also detected in 17 seawater samples (out of 34) using solid phase adsorption toxin tracking devices (0.3 to 0.9 µg/kg-resin). Pinnatoxin G and SPX-1 were confirmed with both low and high resolution (<2 ppm) mass spectrometry by comparison of the response with that from reference standards. For other analogs without reference standards, we applied a strategy combining low resolution MS with a triple quadrupole mass analyzer for a fast and reliable screening, and high resolution MS LTQ Orbitrap® for unambiguous confirmation. The advantages and limitations of using high resolution MS without reference standards were discussed. Full article
(This article belongs to the Special Issue Emerging Marine Toxins)
Open AccessReview Mass Spectrometry Methodology in Lipid Analysis
by , , , , , and
Int. J. Mol. Sci. 2014, 15(6), 10492-10507; doi:10.3390/ijms150610492
Received: 22 April 2014 / Revised: 22 May 2014 / Accepted: 28 May 2014 / Published: 11 June 2014
Cited by 12 | Viewed by 1993 | PDF Full-text (1591 KB) | HTML Full-text | XML Full-text
Abstract
Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However,
[...] Read more.
Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics technology greatly push forward the study of lipidomics. Among them, mass spectrometry (MS) is the most important technology for lipid analysis. In this review, the methodology based on MS for lipid analysis was introduced. It is believed that along with the rapid development of MS and its further applications to lipid analysis, more functional lipids will be identified as biomarkers and therapeutic targets and for the study of the mechanisms of disease. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
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Open AccessArticle The Application of an Emerging Technique for Protein–Protein Interaction Interface Mapping: The Combination of Photo-Initiated Cross-Linking Protein Nanoprobes with Mass Spectrometry
by , , , , and
Int. J. Mol. Sci. 2014, 15(6), 9224-9241; doi:10.3390/ijms15069224
Received: 17 January 2014 / Revised: 6 May 2014 / Accepted: 9 May 2014 / Published: 26 May 2014
Cited by 6 | Viewed by 1869 | PDF Full-text (1150 KB) | HTML Full-text | XML Full-text
Abstract
Protein–protein interaction was investigated using a protein nanoprobe capable of photo-initiated cross-linking in combination with high-resolution and tandem mass spectrometry. This emerging experimental approach introduces photo-analogs of amino acids within a protein sequence during its recombinant expression, preserves native protein structure and is
[...] Read more.
Protein–protein interaction was investigated using a protein nanoprobe capable of photo-initiated cross-linking in combination with high-resolution and tandem mass spectrometry. This emerging experimental approach introduces photo-analogs of amino acids within a protein sequence during its recombinant expression, preserves native protein structure and is suitable for mapping the contact between two proteins. The contact surface regions involved in the well-characterized interaction between two molecules of human 14-3-3ζ regulatory protein were used as a model. The employed photo-initiated cross-linking techniques extend the number of residues shown to be within interaction distance in the contact surface of the 14-3-3ζ dimer (Gln8–Met78). The results of this study are in agreement with our previously published data from molecular dynamic calculations based on high-resolution chemical cross-linking data and Hydrogen/Deuterium exchange mass spectrometry. The observed contact is also in accord with the 14-3-3ζ X-ray crystal structure (PDB 3dhr). The results of the present work are relevant to the structural biology of transient interaction in the 14-3-3ζ protein, and demonstrate the ability of the chosen methodology (the combination of photo-initiated cross-linking protein nanoprobes and mass spectrometry analysis) to map the protein-protein interface or regions with a flexible structure. Full article
(This article belongs to the collection Computational, Structural and Spectroscopic Studies of Enzyme Mechanisms, Inhibition and Dynamics)
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Open AccessArticle Access of Hydrogen-Radicals to the Peptide-Backbone as a Measure for Estimating the Flexibility of Proteins Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry
by , , and
Int. J. Mol. Sci. 2014, 15(5), 8428-8442; doi:10.3390/ijms15058428
Received: 12 March 2014 / Revised: 11 April 2014 / Accepted: 30 April 2014 / Published: 13 May 2014
Cited by 4 | Viewed by 1517 | PDF Full-text (1225 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A factor for estimating the flexibility of proteins is described that uses a cleavage method of “in-source decay (ISD)” coupled with matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). The MALDI-ISD spectra of bovine serum albumin (BSA), myoglobin and thioredoxin show discontinuous intense ion
[...] Read more.
A factor for estimating the flexibility of proteins is described that uses a cleavage method of “in-source decay (ISD)” coupled with matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). The MALDI-ISD spectra of bovine serum albumin (BSA), myoglobin and thioredoxin show discontinuous intense ion peaks originating from one-side preferential cleavage at the N-Cα bond of Xxx-Asp, Xxx-Asn, Xxx-Cys and Gly-Xxx residues. Consistent with these observations, Asp, Asn and Gly residues are also identified by other flexibility measures such as B-factor, turn preference, protection and fluorescence decay factors, while Asp, Asn, Cys and Gly residues are identified by turn preference factor based on X-ray crystallography. The results suggest that protein molecules embedded in/on MALDI matrix crystals partly maintain α-helix and that the reason some of the residues are more susceptible to ISD (Asp, Asn, Cys and Gly) and others less so (Ile and Val) is because of accessibility of the peptide backbone to hydrogen-radicals from matrix molecules. The hydrogen-radical accessibility in MALDI-ISD could therefore be adopted as a factor for measuring protein flexibility. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology) Printed Edition available
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Open AccessArticle Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry Measurement of Caffeine in Caffeine-Laced Pants and in Urine and Skin of a Pants User
by , , , , , and
Cosmetics 2014, 1(2), 82-93; doi:10.3390/cosmetics1020082
Received: 31 January 2014 / Revised: 31 March 2014 / Accepted: 6 April 2014 / Published: 15 April 2014
Viewed by 2130 | PDF Full-text (252 KB) | HTML Full-text | XML Full-text
Abstract
A fast and sensitive ultra-performance liquid chromatography tandem mass spectrometry method was developed for the measurement of caffeine in caffeine-laced pants and in urine and skin of a pants user. The substance and its internal standard (N-ethylnorcotinine) were separated by reversed
[...] Read more.
A fast and sensitive ultra-performance liquid chromatography tandem mass spectrometry method was developed for the measurement of caffeine in caffeine-laced pants and in urine and skin of a pants user. The substance and its internal standard (N-ethylnorcotinine) were separated by reversed phase chromatography with 5 mM ammonium formate pH 3.0 and 0.3% formic acid in acetonitrile mobile phase (83:17 v/v) by isocratic elution and detected by tandem mass spectrometry operated in multiple reaction monitoring mode via positive electrospray ionization. Linearity was studied from 1.4 to100 ng/mL range for urine, from 5 to 100 ng/cotton swab for skin caffeine and from 1.3 to 100 µg/samples for 4 cm2 textile samples. Good determination coefficients (r2 = 0.99) were found in all cases. At three concentrations spanning the linear dynamic ranges of different samples mean recoveries of caffeine were always higher than 80% and intra-assay and inter-assay imprecision and inaccuracy were always better than 105%. For the first time, caffeine content in this cosmetotextile was determined together with the measurement of caffeine released on the user skin, the absorbed amount with resulting urinary concentrations. Full article
(This article belongs to the Special Issue Analytical Methods for Quality Control of Cosmetics)
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Open AccessArticle Towards Lipidomics of Low-Abundant Species for Exploring Tumor Heterogeneity Guided by High-Resolution Mass Spectrometry Imaging
by , , , , , , and
Int. J. Mol. Sci. 2013, 14(12), 24560-24580; doi:10.3390/ijms141224560
Received: 17 October 2013 / Revised: 25 November 2013 / Accepted: 26 November 2013 / Published: 17 December 2013
Cited by 14 | Viewed by 2228 | PDF Full-text (3126 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Many studies have evidenced the main role of lipids in physiological and also pathological processes such as cancer, diabetes or neurodegenerative diseases. The identification and the in situ localization of specific low-abundant lipid species involved in cancer biology are still challenging for both
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Many studies have evidenced the main role of lipids in physiological and also pathological processes such as cancer, diabetes or neurodegenerative diseases. The identification and the in situ localization of specific low-abundant lipid species involved in cancer biology are still challenging for both fundamental studies and lipid marker discovery. In this paper, we report the identification and the localization of specific isobaric minor phospholipids in human breast cancer xenografts by FTICR MALDI imaging supported by histochemistry. These potential candidates can be further confirmed by liquid chromatography coupled with electrospray mass spectrometry (LC-ESI-MS) after extraction from the region of interest defined by MALDI imaging. Finally, this study highlights the importance of characterizing the heterogeneous distribution of low-abundant lipid species, relevant in complex histological samples for biological purposes. Full article
(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)
Open AccessReview Mass Spectrometry Coupled Experiments and Protein Structure Modeling Methods
by and
Int. J. Mol. Sci. 2013, 14(10), 20635-20657; doi:10.3390/ijms141020635
Received: 30 July 2013 / Revised: 17 September 2013 / Accepted: 19 September 2013 / Published: 15 October 2013
Cited by 2 | Viewed by 1728 | PDF Full-text (545 KB) | HTML Full-text | XML Full-text
Abstract
With the accumulation of next generation sequencing data, there is increasing interest in the study of intra-species difference in molecular biology, especially in relation to disease analysis. Furthermore, the dynamics of the protein is being identified as a critical factor in its function.
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With the accumulation of next generation sequencing data, there is increasing interest in the study of intra-species difference in molecular biology, especially in relation to disease analysis. Furthermore, the dynamics of the protein is being identified as a critical factor in its function. Although accuracy of protein structure prediction methods is high, provided there are structural templates, most methods are still insensitive to amino-acid differences at critical points that may change the overall structure. Also, predicted structures are inherently static and do not provide information about structural change over time. It is challenging to address the sensitivity and the dynamics by computational structure predictions alone. However, with the fast development of diverse mass spectrometry coupled experiments, low-resolution but fast and sensitive structural information can be obtained. This information can then be integrated into the structure prediction process to further improve the sensitivity and address the dynamics of the protein structures. For this purpose, this article focuses on reviewing two aspects: the types of mass spectrometry coupled experiments and structural data that are obtainable through those experiments; and the structure prediction methods that can utilize these data as constraints. Also, short review of current efforts in integrating experimental data in the structural modeling is provided. Full article
(This article belongs to the collection Protein Folding)
Open AccessTechnical Note A Computational Drug Metabolite Detection Using the Stable Isotopic Mass-Shift Filtering with High Resolution Mass Spectrometry in Pioglitazone and Flurbiprofen
by , , , , and
Int. J. Mol. Sci. 2013, 14(10), 19716-19730; doi:10.3390/ijms141019716
Received: 22 July 2013 / Revised: 4 September 2013 / Accepted: 9 September 2013 / Published: 30 September 2013
Cited by 2 | Viewed by 1976 | PDF Full-text (2106 KB) | HTML Full-text | XML Full-text
Abstract
The identification of metabolites in drug discovery is important. At present, radioisotopes and mass spectrometry are both widely used. However, rapid and comprehensive identification is still laborious and difficult. In this study, we developed new analytical software and employed a stable isotope as
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The identification of metabolites in drug discovery is important. At present, radioisotopes and mass spectrometry are both widely used. However, rapid and comprehensive identification is still laborious and difficult. In this study, we developed new analytical software and employed a stable isotope as a tool to identify drug metabolites using mass spectrometry. A deuterium-labeled compound and non-labeled compound were both metabolized in human liver microsomes and analyzed by liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS). We computationally aligned two different MS data sets and filtered ions having a specific mass-shift equal to masses of labeled isotopes between those data using our own software. For pioglitazone and flurbiprofen, eight and four metabolites, respectively, were identified with calculations of mass and formulas and chemical structural fragmentation analysis. With high resolution MS, the approach became more accurate. The approach detected two unexpected metabolites in pioglitazone, i.e., the hydroxypropanamide form and the aldehyde hydrolysis form, which other approaches such as metabolite-biotransformation list matching and mass defect filtering could not detect. We demonstrated that the approach using computational alignment and stable isotopic mass-shift filtering has the ability to identify drug metabolites and is useful in drug discovery. Full article
(This article belongs to the Special Issue Xenobiotic Metabolism)
Open AccessArticle Electrospray Quadrupole Travelling Wave Ion Mobility Time-of-Flight Mass Spectrometry for the Detection of Plasma Metabolome Changes Caused by Xanthohumol in Obese Zucker (fa/fa) Rats
by , , , , , , , and
Metabolites 2013, 3(3), 701-717; doi:10.3390/metabo3030701
Received: 3 June 2013 / Revised: 1 August 2013 / Accepted: 7 August 2013 / Published: 13 August 2013
Cited by 10 | Viewed by 2487 | PDF Full-text (1085 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study reports on the use of traveling wave ion mobility quadrupole time-of-flight (ToF) mass spectrometry for plasma metabolomics. Plasma metabolite profiles of obese Zucker fa/fa rats were obtained after the administration of different oral doses of Xanthohumol; a hop-derived dietary supplement. Liquid
[...] Read more.
This study reports on the use of traveling wave ion mobility quadrupole time-of-flight (ToF) mass spectrometry for plasma metabolomics. Plasma metabolite profiles of obese Zucker fa/fa rats were obtained after the administration of different oral doses of Xanthohumol; a hop-derived dietary supplement. Liquid chromatography coupled data independent tandem mass spectrometry (LC-MSE) and LC-ion mobility spectrometry (IMS)-MSE acquisitions were conducted in both positive and negative modes using a Synapt G2 High Definition Mass Spectrometry (HDMS) instrument. This method provides identification of metabolite classes in rat plasma using parallel alternating low energy and high energy collision spectral acquisition modes. Data sets were analyzed using pattern recognition methods. Statistically significant (p < 0.05 and fold change (FC) threshold > 1.5) features were selected to identify the up-/down-regulated metabolite classes. Ion mobility data visualized using drift scope software provided a graphical read-out of differences in metabolite classes. Full article
(This article belongs to the Special Issue Response to Environment and Stress Metabolism)
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Open AccessArticle Metabolic Profiling of Plasma from Benign and Malignant Pulmonary Nodules Patients Using Mass Spectrometry-Based Metabolomics
by , , , and
Metabolites 2013, 3(3), 539-551; doi:10.3390/metabo3030539
Received: 3 May 2013 / Revised: 7 June 2013 / Accepted: 24 June 2013 / Published: 4 July 2013
Cited by 5 | Viewed by 2342 | PDF Full-text (637 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Solitary pulmonary nodule (SPN or coin lesion) is a mass in the lung and can be commonly found in chest X-rays or computerized tomography (CT) scans. However, despite the advancement of imaging technologies, it is still difficult to distinguish malignant cancer from benign
[...] Read more.
Solitary pulmonary nodule (SPN or coin lesion) is a mass in the lung and can be commonly found in chest X-rays or computerized tomography (CT) scans. However, despite the advancement of imaging technologies, it is still difficult to distinguish malignant cancer from benign SPNs. Here we investigated the metabolic profiling of patients with benign and malignant pulmonary nodules. A combination of gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) was used to profile the plasma metabolites in 17 patients with malignant SPNs, 15 patients with benign SPNs and 20 healthy controls. The metabolic profiles were assayed using OPLS-DA, and further analyzed to identify marker metabolites related to diseases. Both GC/MS- and LC/MS-derived models showed clear discriminations in metabolic profiles among three groups. It was found that 63 metabolites (12 from GC/MS, 51 from LC/MS) contributed to the differences. Of these, 48 metabolites showed same change trend in both malignant and benign SPNs as compared with healthy controls, indicating some common pathways including inflammation and oxidative injury shared by two diseases. In contrast, 14 metabolites constituted distinct profiles that differentiated malignant from benign SPNs, which might be a unique biochemical feature associated with lung cancer. Overall, our data suggested that integration of two highly sensitive and complementary metabolomics platforms could enable a comprehensive metabolic profiling and assist in discrimination malignant from benign SPNs. Full article
(This article belongs to the Special Issue Cancer Metabolomics)
Open AccessConcept Paper Quantification of High-Molecular Weight Protein Platforms by AQUA Mass Spectrometry as Exemplified for the CD95 Death-Inducing Signaling Complex (DISC)
by , , and
Cells 2013, 2(3), 476-495; doi:10.3390/cells2030476
Received: 8 May 2013 / Revised: 29 May 2013 / Accepted: 19 June 2013 / Published: 27 June 2013
Cited by 4 | Viewed by 2380 | PDF Full-text (2075 KB) | HTML Full-text | XML Full-text
Abstract
Contemporary quantitative mass spectrometry provides fascinating opportunities in defining the stoichiometry of high-molecular weight complexes or multiprotein platforms. The composition stoichiometry of multiprotein platforms is a key to understand the regulation of complex signaling pathways and provides a basis for constructing models in
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Contemporary quantitative mass spectrometry provides fascinating opportunities in defining the stoichiometry of high-molecular weight complexes or multiprotein platforms. The composition stoichiometry of multiprotein platforms is a key to understand the regulation of complex signaling pathways and provides a basis for constructing models in systems biology. Here we present an improved AQUA technique workflow that we adapted for the quantitative mass spectrometry analysis of the stoichiometry of the CD95 (Fas/APO-1) death inducing signaling complex (DISC). The DISC is a high-molecular weight platform essential for the initiation of CD95-mediated apoptotic and non-apoptotic responses. For protein quantification, CD95 DISCs were immunoprecipitated and proteins in the immunoprecipitations were separated by one-dimensional gel electrophoresis, followed by protein quantification using the AQUA technique. We will discuss in detail AQUA analysis of the CD95 DISC focusing on the key issues of this methodology, i.e., selection and validation of AQUA peptides. The application of this powerful method allowed getting new insights into mechanisms of procaspase-8 activation at the DISC and apoptosis initiation [1]. Here we discuss the AQUA methodology adapted by us for the analysis of the CD95 DISC in more detail. This approach paves the way for the successful quantification of multiprotein complexes and thereby delineating the intrinsic details of molecular interactions. Full article
(This article belongs to the Special Issue Successes of Systems Biology and Future Challenges)
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Open AccessReview Current Status and Future Perspectives of Mass Spectrometry Imaging
by , , and
Int. J. Mol. Sci. 2013, 14(6), 11277-11301; doi:10.3390/ijms140611277
Received: 12 April 2013 / Revised: 9 May 2013 / Accepted: 13 May 2013 / Published: 28 May 2013
Cited by 18 | Viewed by 2980 | PDF Full-text (1112 KB) | HTML Full-text | XML Full-text
Abstract
Mass spectrometry imaging is employed for mapping proteins, lipids and metabolites in biological tissues in a morphological context. Although initially developed as a tool for biomarker discovery by imaging the distribution of protein/peptide in tissue sections, the high sensitivity and molecular specificity of
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Mass spectrometry imaging is employed for mapping proteins, lipids and metabolites in biological tissues in a morphological context. Although initially developed as a tool for biomarker discovery by imaging the distribution of protein/peptide in tissue sections, the high sensitivity and molecular specificity of this technique have enabled its application to biomolecules, other than proteins, even in cells, latent finger prints and whole organisms. Relatively simple, with no requirement for labelling, homogenization, extraction or reconstitution, the technique has found a variety of applications in molecular biology, pathology, pharmacology and toxicology. By discriminating the spatial distribution of biomolecules in serial sections of tissues, biomarkers of lesions and the biological responses to stressors or diseases can be better understood in the context of structure and function. In this review, we have discussed the advances in the different aspects of mass spectrometry imaging processes, application towards different disciplines and relevance to the field of toxicology. Full article
(This article belongs to the collection Advances in Proteomic Research)
Open AccessReview Mass Spectrometry-Based Proteomics for the Analysis of Chromatin Structure and Dynamics
by , , and
Int. J. Mol. Sci. 2013, 14(3), 5402-5431; doi:10.3390/ijms14035402
Received: 7 November 2012 / Revised: 24 January 2013 / Accepted: 20 February 2013 / Published: 6 March 2013
Cited by 20 | Viewed by 2769 | PDF Full-text (539 KB) | HTML Full-text | XML Full-text
Abstract
Chromatin is a highly structured nucleoprotein complex made of histone proteins and DNA that controls nearly all DNA-dependent processes. Chromatin plasticity is regulated by different associated proteins, post-translational modifications on histones (hPTMs) and DNA methylation, which act in a concerted manner to enforce
[...] Read more.
Chromatin is a highly structured nucleoprotein complex made of histone proteins and DNA that controls nearly all DNA-dependent processes. Chromatin plasticity is regulated by different associated proteins, post-translational modifications on histones (hPTMs) and DNA methylation, which act in a concerted manner to enforce a specific “chromatin landscape”, with a regulatory effect on gene expression. Mass Spectrometry (MS) has emerged as a powerful analytical strategy to detect histone PTMs, revealing interplays between neighbouring PTMs and enabling screens for their readers in a comprehensive and quantitative fashion. Here we provide an overview of the recent achievements of state-of-the-art mass spectrometry-based proteomics for the detailed qualitative and quantitative characterization of histone post-translational modifications, histone variants, and global interactomes at specific chromatin regions. This synopsis emphasizes how the advances in high resolution MS, from “Bottom Up” to “Top Down” analysis, together with the uptake of quantitative proteomics methods by chromatin biologists, have made MS a well-established method in the epigenetics field, enabling the acquisition of original information, highly complementary to that offered by more conventional, antibody-based, assays. Full article
(This article belongs to the collection Advances in Proteomic Research)
Open AccessReview The Proteomics Big Challenge for Biomarkers and New Drug-Targets Discovery
by , , and
Int. J. Mol. Sci. 2012, 13(11), 13926-13948; doi:10.3390/ijms131113926
Received: 24 September 2012 / Revised: 17 October 2012 / Accepted: 25 October 2012 / Published: 29 October 2012
Cited by 22 | Viewed by 2897 | PDF Full-text (877 KB) | HTML Full-text | XML Full-text
Abstract
In the modern process of drug discovery, clinical, functional and chemical proteomics can converge and integrate synergies. Functional proteomics explores and elucidates the components of pathways and their interactions which, when deregulated, lead to a disease condition. This knowledge allows the design of
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In the modern process of drug discovery, clinical, functional and chemical proteomics can converge and integrate synergies. Functional proteomics explores and elucidates the components of pathways and their interactions which, when deregulated, lead to a disease condition. This knowledge allows the design of strategies to target multiple pathways with combinations of pathway-specific drugs, which might increase chances of success and reduce the occurrence of drug resistance. Chemical proteomics, by analyzing the drug interactome, strongly contributes to accelerate the process of new druggable targets discovery. In the research area of clinical proteomics, proteome and peptidome mass spectrometry-profiling of human bodily fluid (plasma, serum, urine and so on), as well as of tissue and of cells, represents a promising tool for novel biomarker and eventually new druggable targets discovery. In the present review we provide a survey of current strategies of functional, chemical and clinical proteomics. Major issues will be presented for proteomic technologies used for the discovery of biomarkers for early disease diagnosis and identification of new drug targets. Full article
(This article belongs to the collection Advances in Proteomic Research)
Open AccessArticle Methods for Identification of CA125 from Ovarian Cancer Ascites by High Resolution Mass Spectrometry
by , , and
Int. J. Mol. Sci. 2012, 13(8), 9942-9958; doi:10.3390/ijms13089942
Received: 15 May 2012 / Revised: 11 July 2012 / Accepted: 24 July 2012 / Published: 9 August 2012
Cited by 7 | Viewed by 2200 | PDF Full-text (589 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
CA125 is the most widely used tumour marker in ovarian cancer with unsatisfactory sensitivity and specificity especially at early stage. It is quantified by antibody-based immunoassays; however different molecular weight isoforms have been described in the literature which have never been validated by
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CA125 is the most widely used tumour marker in ovarian cancer with unsatisfactory sensitivity and specificity especially at early stage. It is quantified by antibody-based immunoassays; however different molecular weight isoforms have been described in the literature which have never been validated by mass spectrometry, potentially affecting the diagnostic accuracy and clinical reliability of the test. In this study, CA125 was detected by Western blot and its identity confirmed by mass spectrometry. Two-dimensional (2D) gel electrophoresis in combination with mass spectrometry revealed that positive Western blot signals up to 500 kDa are most likely false-positive interactions of M11-like and OC125-like antibodies. Fibronectin, identified as one of these false-positive interaction partners, increased the reading for CA125 in a first generation ELISA significantly (p = 0.02). The existence of low-molecular weight isoforms of CA125 is therefore questionable and is most likely reflecting cross-reactivity of the antibodies with other proteins. This would explain the conflicting reports on the molecular structure of CA125 and also the inconsistency of CA125 levels by different ELISAs. Our results are also the first steps towards a mass spectrometric assay for CA125 quantification, which would improve sensitivity and reliability. Full article
(This article belongs to the Special Issue Cancer Molecules in Ovarian Cancer 2012)
Open AccessReview Targeted Chiral Analysis of Bioactive Arachidonic Acid Metabolites Using Liquid-Chromatography-Mass Spectrometry
by and
Metabolites 2012, 2(2), 337-365; doi:10.3390/metabo2020337
Received: 1 March 2012 / Revised: 2 April 2012 / Accepted: 9 April 2012 / Published: 20 April 2012
Cited by 6 | Viewed by 2434 | PDF Full-text (943 KB) | HTML Full-text | XML Full-text
Abstract
A complex structurally diverse series of eicosanoids arises from the metabolism of arachidonic acid. The metabolic profile is further complicated by the enantioselectivity of eicosanoid formation and the variety of regioisomers that arise. In order to investigate the metabolism of arachidonic acid in
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A complex structurally diverse series of eicosanoids arises from the metabolism of arachidonic acid. The metabolic profile is further complicated by the enantioselectivity of eicosanoid formation and the variety of regioisomers that arise. In order to investigate the metabolism of arachidonic acid in vitro or in vivo, targeted methods are advantageous in order to distinguish between the complex isomeric mixtures that can arise by different metabolic pathways. Over the last several years this targeted approach has become more popular, although there are still relatively few examples where chiral targeted approaches have been employed to directly analyze complex enantiomeric mixtures. To efficiently conduct targeted eicosanoid analyses, LC separations are coupled with collision induced dissociation (CID) and tandem mass spectrometry (MS/MS). Product ion profiles are often diagnostic for particular regioisomers. The highest sensitivity that can be achieved involves the use of selected reaction monitoring/mass spectrometry (SRM/MS); whereas the highest specificity is obtained with an SRM transitions between an intense parent ion, which contains the intact molecule (M) and a structurally significant product ion. This review article provides an overview of arachidonic acid metabolism and targeted chiral methods that have been utilized for the analysis of the structurally diverse eicosanoids that arise. Full article
(This article belongs to the Special Issue Analytical Techniques in Metabolomics)
Open AccessReview Mass Spectrometry Based Lipidomics: An Overview of Technological Platforms
by , , and
Metabolites 2012, 2(1), 19-38; doi:10.3390/metabo2010019
Received: 23 November 2011 / Revised: 22 December 2011 / Accepted: 24 December 2011 / Published: 5 January 2012
Cited by 40 | Viewed by 3586 | PDF Full-text (411 KB) | HTML Full-text | XML Full-text
Abstract
One decade after the genomic and the proteomic life science revolution, new ‘omics’ fields are emerging. The metabolome encompasses the entity of small molecules—Most often end products of a catalytic process regulated by genes and proteins—with the lipidome being its fat soluble subdivision.
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One decade after the genomic and the proteomic life science revolution, new ‘omics’ fields are emerging. The metabolome encompasses the entity of small molecules—Most often end products of a catalytic process regulated by genes and proteins—with the lipidome being its fat soluble subdivision. Within recent years, lipids are more and more regarded not only as energy storage compounds but also as interactive players in various cellular regulation cycles and thus attain rising interest in the bio-medical community. The field of lipidomics is, on one hand, fuelled by analytical technology advances, particularly mass spectrometry and chromatography, but on the other hand new biological questions also drive analytical technology developments. Compared to fairly standardized genomic or proteomic high-throughput protocols, the high degree of molecular heterogeneity adds a special analytical challenge to lipidomic analysis. In this review, we will take a closer look at various mass spectrometric platforms for lipidomic analysis. We will focus on the advantages and limitations of various experimental setups like ‘shotgun lipidomics’, liquid chromatography—Mass spectrometry (LC-MS) and matrix assisted laser desorption ionization-time of flight (MALDI-TOF) based approaches. We will also examine available software packages for data analysis, which nowadays is in fact the rate limiting step for most ‘omics’ workflows. Full article
(This article belongs to the Special Issue Lipidomics)
Open AccessReview Accurate Quantification of Lipid Species by Electrospray Ionization Mass Spectrometry — Meets a Key Challenge in Lipidomics
by and
Metabolites 2011, 1(1), 21-40; doi:10.3390/metabo1010021
Received: 8 October 2011 / Revised: 2 November 2011 / Accepted: 4 November 2011 / Published: 11 November 2011
Cited by 51 | Viewed by 3023 | PDF Full-text (223 KB) | HTML Full-text | XML Full-text
Abstract
Electrospray ionization mass spectrometry (ESI-MS) has become one of the most popular and powerful technologies to identify and quantify individual lipid species in lipidomics. Meanwhile, quantitative analysis of lipid species by ESI-MS has also become a major obstacle to meet the challenges of
[...] Read more.
Electrospray ionization mass spectrometry (ESI-MS) has become one of the most popular and powerful technologies to identify and quantify individual lipid species in lipidomics. Meanwhile, quantitative analysis of lipid species by ESI-MS has also become a major obstacle to meet the challenges of lipidomics. Herein, we discuss the principles, advantages, and possible limitations of different mass spectrometry-based methodologies for lipid quantification, as well as a few practical issues important for accurate quantification of individual lipid species. Accordingly, accurate quantification of individual lipid species, one of the key challenges in lipidomics, can be practically met. Full article
(This article belongs to the Special Issue Lipidomics)
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Open AccessReview MALDI Imaging Mass Spectrometry (MALDI-IMS)―Application of Spatial Proteomics for Ovarian Cancer Classification and Diagnosis
by , , , and
Int. J. Mol. Sci. 2011, 12(1), 773-794; doi:10.3390/ijms12010773
Received: 1 December 2010 / Revised: 10 January 2011 / Accepted: 17 January 2011 / Published: 21 January 2011
Cited by 52 | Viewed by 9188 | PDF Full-text (616 KB) | HTML Full-text | XML Full-text
Abstract
MALDI imaging mass spectrometry (MALDI-IMS) allows acquisition of mass data for metabolites, lipids, peptides and proteins directly from tissue sections. IMS is typically performed either as a multiple spot profiling experiment to generate tissue specific mass profiles, or a high resolution imaging experiment
[...] Read more.
MALDI imaging mass spectrometry (MALDI-IMS) allows acquisition of mass data for metabolites, lipids, peptides and proteins directly from tissue sections. IMS is typically performed either as a multiple spot profiling experiment to generate tissue specific mass profiles, or a high resolution imaging experiment where relative spatial abundance for potentially hundreds of analytes across virtually any tissue section can be measured. Crucially, imaging can be achieved without prior knowledge of tissue composition and without the use of antibodies. In effect MALDI-IMS allows generation of molecular data which complement and expand upon the information provided by histology including immuno-histochemistry, making its application valuable to both cancer biomarker research and diagnostics. The current state of MALDI-IMS, key biological applications to ovarian cancer research and practical considerations for analysis of peptides and proteins on ovarian tissue are presented in this review. Full article
(This article belongs to the Special Issue Cancer Molecules in Ovarian Cancer)
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Open AccessReview Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry
by , , and
Int. J. Mol. Sci. 2010, 11(12), 5040-5055; doi:10.3390/ijms11125040
Received: 10 November 2010 / Revised: 25 November 2010 / Accepted: 27 November 2010 / Published: 7 December 2010
Cited by 31 | Viewed by 5195 | PDF Full-text (372 KB) | HTML Full-text | XML Full-text
Abstract
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful tool that enables the simultaneous detection and identification of biomolecules in analytes. MALDI-imaging mass spectrometry (MALDI-IMS) is a two-dimensional MALDI-mass spectrometric technique used to visualize the spatial distribution of biomolecules without extraction, purification, separation,
[...] Read more.
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful tool that enables the simultaneous detection and identification of biomolecules in analytes. MALDI-imaging mass spectrometry (MALDI-IMS) is a two-dimensional MALDI-mass spectrometric technique used to visualize the spatial distribution of biomolecules without extraction, purification, separation, or labeling of biological samples. MALDI-IMS has revealed the characteristic distribution of several biomolecules, including proteins, peptides, amino acids, lipids, carbohydrates, and nucleotides, in various tissues. The versatility of MALDI-IMS has opened a new frontier in several fields such as medicine, agriculture, biology, pharmacology, and pathology. MALDI-IMS has a great potential for discovery of unknown biomarkers. In this review, we describe the methodology and applications of MALDI-IMS for biological samples. Full article
(This article belongs to the Special Issue Biomarkers)
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Open AccessCommunication Real-Time Particle Mass Spectrometry Based on Resonant Micro Strings
by , and
Sensors 2010, 10(9), 8092-8100; doi:10.3390/s100908092
Received: 10 July 2010 / Revised: 30 July 2010 / Accepted: 15 August 2010 / Published: 27 August 2010
Cited by 40 | Viewed by 5680 | PDF Full-text (7620 KB) | HTML Full-text | XML Full-text
Abstract
Micro- and nanomechanical resonators are widely being used as mass sensors due to their unprecedented mass sensitivity. We present a simple closed-form expression which allows a fast and quantitative calculation of the position and mass of individual particles placed on a micro or
[...] Read more.
Micro- and nanomechanical resonators are widely being used as mass sensors due to their unprecedented mass sensitivity. We present a simple closed-form expression which allows a fast and quantitative calculation of the position and mass of individual particles placed on a micro or nano string by measuring the resonant frequency shifts ofthe first two bending modes. The method has been tested by detecting the mass spectrum of micro particles placed on a micro string. This method enables real-time mass spectrometry necessary for applications such as personal monitoring devices for the assessment of theexposure dose of airborne nanoparticles. Full article
(This article belongs to the Section Chemical Sensors)
Open AccessArticle Qualitative and Quantitative Saponin Contents in Five Sea Cucumbers from the Indian Ocean
by , and
Mar. Drugs 2010, 8(1), 173-189; doi:10.3390/md8010173
Received: 8 January 2010 / Accepted: 19 January 2010 / Published: 21 January 2010
Cited by 39 | Viewed by 8385 | PDF Full-text (260 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
To avoid predation, holothuroids produce feeding-deterrent molecules in their body wall and viscera, the so-called saponins. Five tropical sea cucumber species of the family Holothuriidae were investigated in order to study their saponin content in two different organs, the body wall and the
[...] Read more.
To avoid predation, holothuroids produce feeding-deterrent molecules in their body wall and viscera, the so-called saponins. Five tropical sea cucumber species of the family Holothuriidae were investigated in order to study their saponin content in two different organs, the body wall and the Cuvierian tubules. Mass spectrometry techniques (MALDI- and ESI-MS) were used to detect and analyze saponins. The smallest number of saponins was observed in Holothuria atra, which contained a total of four congeners, followed by Holothuria leucospilota, Pearsonothuria graeffei and Actinopyga echinites with six, eight and ten congeners, respectively. Bohadschia subrubra revealed the highest saponin diversity (19 congeners). Saponin mixtures also varied between the two body compartments within a given animal. A semi-quantitative approach completed these results and showed that a high diversity of saponins is not particularly correlated to a high saponin concentration. Although the complexity of the saponin mixtures described makes the elucidation of their respective biological roles difficult, the comparisons between species and between body compartments give some clues about how these molecules may act as predator repellents. Full article
(This article belongs to the Special Issue Marine Biotoxins: Novel Issues about Old Compounds)
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