ijms-logo

Journal Browser

Journal Browser

Special Issue "New Insights on Mass Spectometry Applied to Bioscience"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: 31 March 2022.

Special Issue Editors

Dr. Rene Zahedi
E-Mail Website
Guest Editor
Skolkovo Institute of Science and Technology, 121205 Moscow, Russia
Interests: Proteomes; Cancers
Prof. Dr. Christoph Borchers
E-Mail
Guest Editor
Department Oncology, Faculty of Medicine, McGill University, Montreal, QC H3G 1Y6, Canada
Interests: proteomics; biomarkers; metabolomics; structural proteomics; clinical diagnostics

Special Issue Information

This Special Issue will contain manuscripts on the latest mass spectrometry-based technologies and techniques, including newly developed approaches and methods applied to bioscience. Both reviews and original articles on novel instrumental mass spectrometric approaches in biosciences, quantitative proteomics, and single-cell proteomics will be included. Of particular interest are approaches which can provide highly multiplexed protein quantitation with rapid analysis times. 

This issue will also contain articles on the latest developments in peptide and protein imaging, novel methods in structural proteomics, proteogenomics, and proteomulti-omics, and clinical proteomics. 

The articles in this Special Issue shall demonstrate the potential of these techniques and technologies to answer important biological, biochemical, biomedical, and clinical questions and will demonstrate to the readers the valuable and continuing contribution of modern mass spectrometry to bioscience.

 

Dr. Rene Zahedi
Prof. Dr. Christoph Borchers
Guest Editors

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 papers will be 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Mass Spectometry
  • Single-Cell 
  • Proteomics
  • Biosciences
  • Protein Imaging 
  • Omics

Published Papers (1 paper)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Article
Mass Spectrometric and Bio-Computational Binding Strength Analysis of Multiply Charged RNAse S Gas-Phase Complexes Obtained by Electrospray Ionization from Varying In-Solution Equilibrium Conditions
Int. J. Mol. Sci. 2021, 22(19), 10183; https://doi.org/10.3390/ijms221910183 - 22 Sep 2021
Viewed by 321
Abstract
We investigated the influence of a solvent’s composition on the stability of desorbed and multiply charged RNAse S ions by analyzing the non-covalent complex’s gas-phase dissociation processes. RNAse S was dissolved in electrospray ionization-compatible buffers with either increasing organic co-solvent content or different [...] Read more.
We investigated the influence of a solvent’s composition on the stability of desorbed and multiply charged RNAse S ions by analyzing the non-covalent complex’s gas-phase dissociation processes. RNAse S was dissolved in electrospray ionization-compatible buffers with either increasing organic co-solvent content or different pHs. The direct transition of all the ions and the evaporation of the solvent from all the in-solution components of RNAse S under the respective in-solution conditions by electrospray ionization was followed by a collision-induced dissociation of the surviving non-covalent RNAse S complex ions. Both types of changes of solvent conditions yielded in mass spectrometrically observable differences of the in-solution complexation equilibria. Through quantitative analysis of the dissociation products, i.e., from normalized ion abundances of RNAse S, S-protein, and S-peptide, the apparent kinetic and apparent thermodynamic gas-phase complex properties were deduced. From the experimental data, it is concluded that the stability of RNAse S in the gas phase is independent of its in-solution equilibrium but is sensitive to the complexes’ gas-phase charge states. Bio-computational in-silico studies showed that after desolvation and ionization by electrospray, the remaining binding forces kept the S-peptide and S-protein together in the gas phase predominantly by polar interactions, which indirectly stabilized the in-bulk solution predominating non-polar intermolecular interactions. As polar interactions are sensitive to in-solution protonation, bio-computational results provide an explanation of quantitative experimental data with single amino acid residue resolution. Full article
(This article belongs to the Special Issue New Insights on Mass Spectometry Applied to Bioscience)
Show Figures

Figure 1

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Epitope structure and affinity determination of protein-antibody and DNA-aptamer interactions by SPR- MALDI mass spectrometry combination
Authors: Lupu
Affiliation: Centre for Analytical Biochemistry and Biomedical Mass Spectrometry

Title: Structure identification and affinity determination of protein-antibody and aptamer- epitopes by biosensor-mass spectrometry combination
Authors: Loredana-Mirela Lupu1*; Pascal Wiegand1*; Daria Holdschick1; Delia Mihoc1; Stefan Maeser1*; Friedemann Völklein2; Ebrahim Malek1; Frederik Barka3; Sascha Knauer4; Christina Uth4; Julia Hennermann5; Wolfgang Kleinekofort1; 2; Andreas Hahn6; Günes Barka3; Michael Przybylski1; 2**
Affiliation: 1Steinbeis Transfer Centre for Biopolymer Analysis and Biomedical Mass Spectrometry, and Centre for Analytical Biochemistry, Marktstrasse 29, 65428, Rüsselsheim am Main, Germany 2 Rhein Main University, Department of Engineering & Institute for Microtechnologies (IMTECH), 65428 Rüsselsheim am Main, Germany 3Sunchrom GmbH, Industriestr. 27, 61381 Friedrichsdorf, Germany 4Sulfotools GmbH, Bahnhofsplatz 1, 65428 Rüsselsheim am Main, Germany 5Universitätsmedizin Mainz, Department of Pediatrics, 55130 Mainz, Germany 6Universität Giessen, Neuropediatric Department, Feulgenstraße 10-12, 35389 Giessen, Germany
Abstract: The combination of analytical methods for the molecular characterization of new diagnostic or therapeutic targets has recently gained high interest. Here we describe the structure identification and affinity quantification of protein interactions with antibodies and DNA-aptamers by MALDI mass spectrometry (MS) in combination with surface plasmon resonance (SPR) biosensor analysis. In a first step the binding constant (KD) determination of a protein-antibody complex is performed by applying the protein antigen to an SPR chip containing a functionalized antibody or DNA-aptamer surface. A proteolytic peptide mixture is then applied to the SPR chip. Following the removal of nonbinding material by washing, the epitope(s) peptide(s) are eluted onto a sample target plate and identified by MALDI-MS. The SPR-MS combination was applied to epitope analyses of a number of affinity pairs. Distinct epitope peptides were identified for the cardiac biomarker myoglobin (MG) both from monoclonal and polyclonal antibodies. Immobilization of antibodies on SPR chips using protein G substantially improved surface fixation and antibody stabilities for mass spectrometric epitope identifications and affinity determinations by SPR. Affinity binding constants were determined for equine and human MG, providing direct molecular assessment of cross immunoreactivities. Moreover, epitopes were successfully determined for protein G- immobilized polyclonal antibodies from biological material, such as epitopes from patient antisera upon enzyme replacement therapy of lysosomal diseases, and from patients upon therapy with the antidrug antibody Adalimumab. Mass spectrometric epitope identifications were obtained for linear, as well as for assembled (“conformational”) antibody epitopes, such as for the polypeptide chemokine Interleukin-8. Using the SPR-MS combination, linear and assembled epitopes were identified for DNA-aptamer- interaction complexes with the tumor diagnostic protein C-Met. These results demonstrate the powerful combination tool of SPR and MALDI-MS for the molecular determination of protein interaction complexes.

Title: Mass spectrometric and bio-computational analysis of multiply charged RNAse S gas phase complexes obtained by electrospray ionization from varying in-solution equilibrium conditions.
Authors: Mickael Glocker
Affiliation: Proteome Center Rostock Department for Proteome Research Institute of Immunology Medical Faculty and Natural Science Faculty University of Rostock Schillingallee 69 P.O. Box 100 888 18055 Rostock Germany
Abstract: In this research project we investigate the influence of a solvent´s composition on the stability of desorbed and multiply charged RNAse S ions by analyzing gas phase dissociation processes. RNAse S was dissolved in ESI-compatible buffers with either an increasing content of organic co-solvent or with different pH. Direct transition of all ions from the in-solution components is followed after evaporation of the solvent by collision-induced-dissociation of the non-covalent RNAse S complexes and by quantitative analysis of the dissociation products. From normalized ion abundances of RNAse S, S-protein, and S-peptide are determined the apparent kinetic and apparent thermodynamic gas phase complex properties. The stability of RNAse S in the gas phase is independent from the in-solution equilibrium but sensitive to differences in the complexes´ charge states. Biocomputational in-silico studies show that after the desolvation process the remaining binding forces keep the S-peptide and S-protein together predominantly by polar interactions, which stands in agreement with the experimental data.

Title: Rapid and comprehensive discrimination of intact antibodies using multicharge-state collision-induced unfolding
Authors: Zhibin Yin; Xinzhou Wu; Mingyi Du; Dong Chen; Wenyang Zhang; Wenjie Huang; Shijuan Yan
Affiliation: Guangdong Key Laboratory for Crop Germplasm Resources Preservation and Utilization, Agro-biological Gene Research Center, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, China
Abstract: Immunoglobulin G (IgG) antibodies are an important class of biotherapeutics that target various diseases, such as cancers, neurodegenerative disorders, and autoimmune diseases, yet rapid and comprehensive characterization of IgG antibodies remains a great challenge due to heterogeneity, flexibility, and large size. Herein, we demonstrate a simplified multicharge-state collision-induced unfolding (CIU) method for rapid differentiation of four IgG isotypes (IgG1κ, IgG2κ, IgG3κ, and IgG4κ) that differ in terms of the numbers and patterns of disulfide bonds, bypassing tedious single charge-state selection in advance. Using this strategy, the correlation between surface charge states and gas-phase unfolding patterns of IgG antibodies was investigated. The results presented herein reveal that gas-phase unfolding behaviors have a strong dependence on charge states outside IgG surfaces; therefore, multicharge-state CIU analysis of IgG subtypes could offer a great opportunity to gain deeper insights into their gas-phase structural differentiation. The full discrimination of antibody isoforms that possess different disulfide bond numbers and even subtle disulfide bonding patterns can be achieved based on their charge-dependent gas-phase unfolding behaviors and root-mean square deviation (RMSD) in CIU difference spectra. Taken together, the incorporation of all charge states observed in a native IM-MS experiment to CIU analysis could make this strategy sensitive to more subtle structural discrepancies, facilitating the rapid discrimination and evaluation of innovative structurally similar biotherapeutic candidates with unexplored functions.

Title: Affinity purification coupled to stable-isotope dilution LC-MS/MS analysis to discover IgG4 glycosylation profiles for autoimmune pancreatitis
Authors: I-Lin Tsai
Affiliation: Canada
Abstract: Type-I autoimmune pancreatitis is categorized as IgG4 related disease (IgG4-RD) which high concentration of plasma IgG4 is one of the common biomarkers among patients. IgG Fc-glycosylation has been reported to be potential biosignatures for diseases. However, human IgG3 and IgG4 Fc-glycopeptides from Asia populations were found to be isobaric ions when using LC-MS/MS as an analytical tool. In this study, we developed an analytical workflow that coupled affinity purification and stable isotope dilution LC-MS/MS to dissect IgG4 glycosylation profiles for autoimmune pancreatitis. Detailed sample preparation and method validation for absolution quantification of IgG4 and relative quantification of IgG4 glycopeptides were performed followed by the clinical applications.

Title: An Update on Lysosomal Storage Diseases Diagnostic by Multiplexed Mass Spectrometry-Based Approaches
Authors: Laura Darie Ion; Daniela Cristina Dimitriu; Violeta Mangalagiu; Brindusa Alina Petre
Affiliation: 1 Faculty of Chemistry, Alexandru Ioan Cuza University of Iasi, 11 Carol 1st Bvd, 700506 Iasi, Romania; [email protected] (L.D.I) 2 Grigore T. Popa University of Medicine and Pharmacy, Department of Biochemistry, 16 Universitatii Str., 700115, Iasi, Romania; [email protected] (D.C.D) 3 CERNESIM Centre, Institute of Interdisciplinary Research, AlexandruIoanCuza University of Iasi, 11 Carol 1st Bvd, 700506 Iasi, Romania; [email protected] (V.M.) 4 Center for Fundamental Research and Experimental Development in Translation Medicine–TRANSCEND, Regional Institute of Oncology, 700483 Iaşi, Romania * [email protected]; Tel.: +4 0721 805 402
Abstract: Lysosomal storage disorders (LSDs) are a type of inherited metabolic disorders in which biomolecules, such as glycosaminoglycans, lipids, peptides and glycoproteins, accumulate as a particular substrate in lysosomes. These accumulations are caused for the most LSDs by specific individual enzyme deficiencies within the lysosome. Lysosomal storage disorders are defined by clinical manifestations affecting various organs and systems (neurological, muscular, and skeletal) in the body, even if they are frequently asymptomatic at patient birth. Despite the fact that lysosomal storage disorders are incurable, various approaches, including enzyme replacement therapy, hematopoietic stem cell transplantation, or gene therapy are now available and can help individuals by significantly improving their symptoms. Therefore, a timely diagnosis is a critical initial step of the treatment process for the patient. Currently, the state of art in LSDs diagnostic uses in first stage biochemical tests, such as enzymatic activity determinations by fluorimetry or by mass spectrometry (limited cases) with the aid of dry blood spots based on different enzymatic substrates-structures. Moreover, due to its sensitivity, high precision, and ability to screen for an unprecedented number of diseases in a single assay, multiplex tandem mass spectrometry-based enzyme activity assays for newborn screening and diagnosis of lysosomal storage disorders in newborns, have gotten a lot of attention. In this article, (i) we review the current approaches used for simultaneous enzymatic activity determination of LSDs in dried blood spots using multiplex - tandem mass spectrometry; (ii) we explore the need of designing more enzymatic substrates that will give enzymatic products with distinct molecular mass in multiplex-mass spectrometry studies; and (iii) we exemplify the relevance of affinity-mass spectrometry technique as a basis for reversing undesirable immunoreactivity in enzyme replacement therapy.

Back to TopTop