@article{18d67dc1181140499dc9d30e7ab53b65,
title = "Composition and charge state influence on the ion-neutral collision cross sections of protonated N-linked glycopeptides: An experimental and theoretical deconstruction of coulombic repulsion: Vs. charge solvation effects",
abstract = "Ion mobility spectrometry (IMS) is of significant interest as a platform for glycoanalysis. While much attention has been focused on the resolution of isomeric carbohydrates and glycoconjugates, another appealing aspect of IMS is the ability to sort different classes of biomolecules into distinct regions of mass vs. mobility space. This capability has potential to greatly simplify glycoproteomic analyses, as glycosylated and non-glycosylated peptides can be rapidly partitioned in the gas phase. Nevertheless, the physical and chemical characteristics of glycopeptides that dictate their mass vs. mobility loci have yet to be systematically investigated. This report presents an IMS study of model protonated glycopeptide ions with systematically varied oligosaccharide topologies, polypeptide sequences, and charge states. In all, over 110 ion-neutral collision cross sections (CCSs) were measured and analyzed in the context of the physicochemical characteristics of the analytes. Glycan size and composition emerged as a decisive factor in dictating the CCS space occupied by the glycopeptides and exerted this influence in a charge state dependent fashion. Furthermore, elongation of the glycan group was found to either increase or decrease glycopeptide CCSs depending on the ion charge state and the size of the glycan. Molecular dynamics (MD) simulations of the gas phase structures and CCSs of selected glycopeptides revealed that the experimental observations were consistent with a glycan size and charge state dependent interplay between destabilizing coulombic repulsion effects (tending to result in more extended structures) and stabilizing charge solvation effects in which the glycan plays a major role (tending to result in more compact structures). Taken together, these IMS and MD findings suggest the possibility of predicting and delineating glycopeptide-enriched regions of mass vs. mobility space for applications in glycoproteomics.",
author = "Gelb, {Abby S.} and Rui Lai and Hui Li and Dodds, {Eric D.}",
note = "Funding Information: National Institutes of Health, National Institute of General Medical Sciences, supported this work through a Maximizing Investigators' Research Award to E. D. D. (grant number R35GM128926), a fellowship to A. S. G. from the Molecular Mechanisms of Disease Predoctoral Training Program (grant number T32GM107001), and a seed grant to H. L. and E. D. D. from the Nebraska Center for Integrated Biomolecular Communication (grant number P20GM113126). Funding to E. D. D. from the National Science Foundation, Division of Chemistry, through the Chemical Measurement and Imaging Program (grant number 1507989) is also acknowledged. This work was carried out using core facilities supported in part by the National Institutes of Health, National Institute of General Medical Sciences through the Nebraska Center for Integrated Biomolecular Communication (grant number P20GM113126). Computational chemistry calculations were performed using resources at the University of Nebraska Holland Computing Center. Finally, A. S. G. would like to thank Dr. Yuting Huang for valued guidance and mentorship in the early stages of this project. Funding Information: Funding from the National Institutes of Health, National Institute of General Medical Sciences, supported this work through a Maximizing Investigators{\textquoteright} Research Award to E. D. D. (grant number R35GM128926), a fellowship to A. S. G. from the Molecular Mechanisms of Disease Predoctoral Training Program (grant number T32GM107001), and a seed grant to H. L. and E. D. D. from the Nebraska Center for Integrated Biomolecular Communication (grant number P20GM113126). Funding to E. D. D. from the National Science Foundation, Division of Chemistry, through the Chemical Measurement and Imaging Program (grant number 1507989) is also acknowledged. This work was carried out using core facilities supported in part by the National Institutes of Health, National Institute of General Medical Sciences through the Nebraska Center for Integrated Biomolecular Communication (grant number P20GM113126). Computational chemistry calculations were performed using resources at the University of Nebraska Holland Computing Center. Finally, A. S. G. would like to thank Dr. Yuting Huang for valued guidance and mentorship in the early stages of this project. Publisher Copyright: {\textcopyright} 2019 The Royal Society of Chemistry.",
year = "2019",
month = oct,
day = "7",
doi = "10.1039/c9an00875f",
language = "English (US)",
volume = "144",
pages = "5738--5747",
journal = "The Analyst",
issn = "0003-2654",
publisher = "Royal Society of Chemistry",
number = "19",
}