Collision Cross Sections and Ion Mobility Separation of Fragment Ions from Complex N-Glycans

AbstractIon mobility mass spectrometry (IM-MS) holds great potential for structural glycobiology, in particular in its ability to resolve glycan isomers. Generally, IM-MS has largely been applied to intact glycoconjugate ions with reports focusing on the separation of different adduct types. Here, we explore IM separation and report the collision cross section (CCS) of complex type N-glycans and their fragments in negative ion mode following collision-induced dissociation (CID). CCSs of isomeric fragment ions were found, in some cases, to reveal structural details that were not present in CID spectra themselves. Many fragment ions were confirmed as possessing multiple structure, details of which could be obtained by comparing their drift time profiles to different glycans. By using fragmentation both before and after mobility separation, information was gathered on the fragmentation pathways producing some of the ions. These results help demonstrate the utility of IM and will contribute to the growing use of IM-MS for glycomics. Graphical Abstractᅟ

[1]  Santanu Mandal,et al.  Bottom-Up Elucidation of Glycosidic Bond Stereochemistry. , 2017, Analytical chemistry.

[2]  Richard D. Smith,et al.  Enhancing glycan isomer separations with metal ions and positive and negative polarity ion mobility spectrometry-mass spectrometry analyses , 2016, Analytical and Bioanalytical Chemistry.

[3]  Erdmann Rapp,et al.  The minimum information required for a glycomics experiment (MIRAGE) project: sample preparation guidelines for reliable reporting of glycomics datasets. , 2016, Glycobiology.

[4]  P. H. Seeberger,et al.  Identification of carbohydrate anomers using ion mobility–mass spectrometry , 2015, Nature.

[5]  V. Havlíček,et al.  Simple area determination of strongly overlapping ion mobility peaks. , 2017, Analytica chimica acta.

[6]  Larissa S Fenn,et al.  Structural resolution of carbohydrate positional and structural isomers based on gas-phase ion mobility-mass spectrometry. , 2011, Physical chemistry chemical physics : PCCP.

[7]  H. Hill,et al.  Ion mobility-mass spectrometry analysis of isomeric carbohydrate precursor ions , 2009, Analytical and bioanalytical chemistry.

[8]  H. Hill,et al.  Separation of sodiated isobaric disaccharides and trisaccharides using electrospray ionization-atmospheric pressure ion mobility-time of flight mass spectrometry , 2005, Journal of the American Society for Mass Spectrometry.

[9]  D. Harvey Fragmentation of negative ions from carbohydrates: Part 2. Fragmentation of high-mannose N-linked glycans , 2005, Journal of the American Society for Mass Spectrometry.

[10]  M. Rejžek,et al.  Discrimination of epimeric glycans and glycopeptides using IM-MS and its potential for carbohydrate sequencing , 2013, Nature Chemistry.

[11]  J. Trinidad,et al.  Populations of Metal-Glycan Structures Influence MS Fragmentation Patterns , 2014, Journal of The American Society for Mass Spectrometry.

[12]  D. Harvey Fragmentation of negative ions from carbohydrates: Part 3. Fragmentation of hybrid and complex N-linked glycans , 2005, Journal of the American Society for Mass Spectrometry.

[13]  K. Pagel,et al.  Identification of Lewis and Blood Group Carbohydrate Epitopes by Ion Mobility-Tandem-Mass Spectrometry Fingerprinting. , 2017, Analytical chemistry.

[14]  B. Domon,et al.  A systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates , 1988, Glycoconjugate Journal.

[15]  Eric D. Dodds,et al.  Ion mobility studies of carbohydrates as group I adducts: isomer specific collisional cross section dependence on metal ion radius. , 2013, Analytical chemistry.

[16]  Kelly K. Lee,et al.  Site-Specific Mapping of Sialic Acid Linkage Isomers by Ion Mobility Spectrometry. , 2016, Analytical chemistry.

[17]  A. Konijnenberg,et al.  Evaluation of ion mobility for the separation of glycoconjugate isomers due to different types of sialic acid linkage, at the intact glycoprotein, glycopeptide and glycan level. , 2018, Journal of proteomics.

[18]  Louise Royle,et al.  Proposal for a standard system for drawing structural diagrams of N‐ and O‐linked carbohydrates and related compounds , 2009, Proteomics.

[19]  R. Dwek,et al.  A rapid high-resolution high-performance liquid chromatographic method for separating glycan mixtures and analyzing oligosaccharide profiles. , 1996, Analytical biochemistry.

[20]  C. Scarff,et al.  Travelling-wave ion mobility mass spectrometry and negative ion fragmentation of hybrid and complex N-glycans. , 2016, Journal of mass spectrometry : JMS.

[21]  R. Dwek,et al.  Structural and quantitative analysis of N-linked glycans by matrix-assisted laser desorption ionization and negative ion nanospray mass spectrometry. , 2008, Analytical biochemistry.

[22]  C. Scarff,et al.  Estimating collision cross sections of negatively charged N-glycans using traveling wave ion mobility-mass spectrometry. , 2014, Analytical Chemistry.

[23]  Erdmann Rapp,et al.  The Minimum Information Required for a Glycomics Experiment (MIRAGE) Project: Improving the Standards for Reporting Mass-spectrometry-based Glycoanalytic Data , 2013, Molecular & Cellular Proteomics.

[24]  William F Siems,et al.  Resolving structural isomers of monosaccharide methyl glycosides using drift tube and traveling wave ion mobility mass spectrometry. , 2012, Analytical chemistry.

[25]  T. Fournier,et al.  Alpha-1-acid glycoprotein. , 2000, Biochimica et biophysica acta.

[26]  Konstantinos Thalassinos,et al.  Characterization of phosphorylated peptides using traveling wave-based and drift cell ion mobility mass spectrometry. , 2009, Analytical chemistry.

[27]  C. Scarff,et al.  Ion Mobility Mass Spectrometry for Extracting Spectra of N-Glycans Directly from Incubation Mixtures Following Glycan Release: Application to Glycans from Engineered Glycoforms of Intact, Folded HIV gp120 , 2011, Journal of the American Society for Mass Spectrometry.

[28]  Jodie L Abrahams,et al.  Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. Reduced glycans. , 2016, Rapid communications in mass spectrometry : RCM.

[29]  Eric D. Dodds,et al.  Ion-neutral collisional cross sections of carbohydrate isomers as divalent cation adducts and their electron transfer products. , 2015, The Analyst.

[30]  Lukasz G. Migas,et al.  Applications of ion mobility mass spectrometry for high throughput, high resolution glycan analysis. , 2016, Biochimica et biophysica acta.

[31]  C. Robinson,et al.  Determining the stoichiometry and interactions of macromolecular assemblies from mass spectrometry , 2007, Nature Protocols.

[32]  R. Dwek,et al.  Identification of highly fucosylated N-linked oligosaccharides from the human parotid gland. , 1998, European journal of biochemistry.

[33]  Cheng Lin,et al.  Separation and Identification of Isomeric Glycans by Selected Accumulation-Trapped Ion Mobility Spectrometry-Electron Activated Dissociation Tandem Mass Spectrometry. , 2016, Analytical chemistry.

[34]  K. Pagel,et al.  Ion mobility separation of deprotonated oligosaccharide isomers - evidence for gas-phase charge migration. , 2016, Chemical communications.

[35]  M. Crispin,et al.  Ion Mobility Mass Spectrometry for Ion Recovery and Clean-Up of MS and MS/MS Spectra Obtained from Low Abundance Viral Samples , 2015, Journal of The American Society for Mass Spectrometry.

[36]  M. Guttman,et al.  Bridging the structural gap of glycoproteomics with ion mobility spectrometry. , 2018, Current opinion in chemical biology.