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Mass Spectrometry in Chemical Biology: Evolving Applications for Small Molecules

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 4857

Special Issue Editor

Organic Synthesis & Mass Spectrometry Lab, University of Mons, 19, avenue Maistriau, B-7000 Mons, Belgium
Interests: organic chemistry; mass spectrometry; structural characterization; gas phase ion chemistry; natural products; macromolecules

Special Issue Information

Dear Colleagues,

Chemical Biology is an emerging discipline combining chemistry and biology. At variance with biochemistry that studies the chemical processes occurring in living organisms, chemical biology is a scientific discipline that studies or manipulates living organisms using chemical tools. Chemical biology is concerned with in vitro and in vivo processes involving small molecules that have been identified or designed for specific objectives. Chemical biology has ramifications in fields as diverse as medicinal chemistry, supramolecular chemistry, bioorganic chemistry, pharmacology, genetics, biochemistry, and metabolic engineering.

One of the main aspects of this research is the identification of small molecules of interest in the living organisms studied. Due to its intrinsic properties, i.e., specificity, sensitivity, and resolution, mass spectrometry has emerged over the last few decades as the technique of choice for the analysis of small molecules within complex biological matrices. The classification of a molecule among “small molecules2 seems a priori very arbitrary, and it is generally accepted that this notion covers all the molecules of low molecular mass (<2 kDa) of endogenous or exogenous origins present in living organisms. Endogenous primary and secondary (specific) metabolites are therefore found among these small molecules. Drugs and their metabolites are also an integral part of this class of molecules.

The detection and identification of small molecules within complex biological matrices requires powerful analytical methods among which mass spectrometry is becoming essential today. Mass spectrometry analysis can be conducted either on extracts­—meaning that the biological matrix has been submitted to specific extraction procedures—or directly on-tissue by preserving the memory of the spatial localization of molecules. The former approach relies on the association of chromatography separation prior to introduction in the source of the mass spectrometer often operating with atmospheric pressure ionization methods such as electrospray ionization. Targeted and non-targeted approaches refer to the targeted search for known compounds or to blind analyses without prerequisite knowledge of the molecules to be searched for. The on-tissue approach is associated with imaging techniques and, at this level, it is the sampling techniques that must be optimized so as not to lose information about the location of the molecules.

In addition to the sampling and ionization of the compounds, their structural identification represents another key aspect of the analysis. Mass spectrometry methods today go beyond the simple determination of the molecular mass of the molecules of interest by recording the exact masses of the corresponding ions. In fact, modern mass spectrometry techniques allow creating precise information on the connectivity of ions, which makes it possible to identify functional groups and to distinguish isomers on the basis of the recording of fragment ions generated from activated precursor ions. Many ion activation methods are developed today and are based on interactions between the ions of interest with molecules or atoms (collision-induced Dissociation), with photons (infrared multiphoton dissociation or ultraviolet dissociation), electrons (electron capture dissociation) or ions of opposite charge (electron transfer dissociation or proton transfer dissociation). In addition, the emergence of techniques such as ion mobility now makes it possible to obtain information on the configuration (cis-trans, stereogenic carbon, etc.) and even the conformation of ions (helices, etc.).

The present Special Issue intends to offer a broad overview of state-of the-art mass spectrometry methods used and developed for chemical-biology-related investigations.

Prof. Dr. Pascal Gerbaux
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • chemical biology
  • mass spectrometry
  • small molecules
  • specific metabolites
  • ion activation
  • targeted and no targeted analysis
  • liquid chromatography
  • MALDI imaging
  • ion mobility

Published Papers (2 papers)

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Research

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11 pages, 845 KiB  
Article
Validation of an HPLC–MS/MS Method for the Determination of Plasma Ticagrelor and Its Active Metabolite Useful for Research and Clinical Practice
by Jennifer Lagoutte-Renosi, Bernard Royer, Vahideh Rabani and Siamak Davani
Molecules 2021, 26(2), 278; https://doi.org/10.3390/molecules26020278 - 08 Jan 2021
Cited by 11 | Viewed by 2199
Abstract
Ticagrelor is an antiplatelet agent which is extensively metabolized in an active metabolite: AR-C124910XX. Ticagrelor antagonizes P2Y12 receptors, but recently, this effect on the central nervous system has been linked to the development of dyspnea. Ticagrelor-related dyspnea has been linked to persistently high [...] Read more.
Ticagrelor is an antiplatelet agent which is extensively metabolized in an active metabolite: AR-C124910XX. Ticagrelor antagonizes P2Y12 receptors, but recently, this effect on the central nervous system has been linked to the development of dyspnea. Ticagrelor-related dyspnea has been linked to persistently high plasma concentrations of ticagrelor. Therefore, there is a need to develop a simple, rapid, and sensitive method for simultaneous determination of ticagrelor and its active metabolite in human plasma to further investigate the link between concentrations of ticagrelor, its active metabolite, and side effects in routine practice. We present here a new method of quantifying both molecules, suitable for routine practice, validated according to the latest Food and Drug Administration (FDA) guidelines, with a good accuracy and precision (<15% respectively), except for the lower limit of quantification (<20%). We further describe its successful application to plasma samples for a population pharmacokinetics study. The simplicity and rapidity, the wide range of the calibration curve (2–5000 µg/L for ticagrelor and its metabolite), and high throughput make a broad spectrum of applications possible for our method, which can easily be implemented for research, or in daily routine practice such as therapeutic drug monitoring to prevent overdosage and occurrence of adverse events in patients. Full article
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Review

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20 pages, 1735 KiB  
Review
Mass Spectrometry for the Monitoring of Lipoprotein Oxidations by Myeloperoxidase in Cardiovascular Diseases
by Catherine Coremans, Cédric Delporte, Frédéric Cotton, Phillipe Van De Borne, Karim Zouaoui Boudjeltia and Pierre Van Antwerpen
Molecules 2021, 26(17), 5264; https://doi.org/10.3390/molecules26175264 - 30 Aug 2021
Cited by 4 | Viewed by 2044
Abstract
Oxidative modifications of HDLs and LDLs by myeloperoxidase (MPO) are regularly mentioned in the context of atherosclerosis. The enzyme adsorbs on protein moieties and locally produces oxidizing agents to modify specific residues on apolipoproteins A-1 and B-100. Oxidation of lipoproteins by MPO (Mox) [...] Read more.
Oxidative modifications of HDLs and LDLs by myeloperoxidase (MPO) are regularly mentioned in the context of atherosclerosis. The enzyme adsorbs on protein moieties and locally produces oxidizing agents to modify specific residues on apolipoproteins A-1 and B-100. Oxidation of lipoproteins by MPO (Mox) leads to dysfunctional Mox-HDLs associated with cholesterol-efflux deficiency, and Mox-LDLs that are no more recognized by the LDL receptor and become proinflammatory. Several modification sites on apoA-1 and B-100 that are specific to MPO activity are described in the literature, which seem relevant in patients with cardiovascular risk. The most appropriate analytical method to assess these modifications is based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). It enables the oxidized forms of apoA-1and apoB-100 to be quantified in serum, in parallel to a quantification of these apolipoproteins. Current standard methods to quantify apolipoproteins are based on immunoassays that are well standardized with good analytical performances despite the cost and the heterogeneity of the commercialized kits. Mass spectrometry can provide simultaneous measurements of quantity and quality of apolipoproteins, while being antibody-independent and directly detecting peptides carrying modifications for Mox-HDLs and Mox-LDLs. Therefore, mass spectrometry is a potential and reliable alternative for apolipoprotein quantitation. Full article
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