Mannose7 Glycan Isomer Characterization by IMS-MS/MS Analysis

Zhu, Feifei; Lee, Sun Young; Valentine, Stephen J.; Reilly, James P.; Clemmer, David E.

doi:10.1007/s13361-012-0491-y

Cited by 67 publications

(67 citation statements)

References 47 publications

(50 reference statements)

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“…40,70,71 This instrument contains a source region that is essentially identical to the one used in the IMS-MS measurements. This ensures sampling of nearly identical ion populations during ESI on these two instruments.…”

Section: Methodsmentioning

confidence: 99%

Populations of Metal-Glycan Structures Influence MS Fragmentation Patterns

Zhu

Glover

Shi

et al. 2014

J. Am. Soc. Mass Spectrom.

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The structures and collision-induced dissociation (CID) fragmentation patterns of the permethylated glycan Man5GlcNAc2 are investigated by a combination of hybrid ion mobility spectrometry (IMS), mass spectrometry (MS), and MS/MS techniques. IMS analysis of eight metal-adducted glycans ([Man5GlcNAc2+M]2+, where M = Mn, Fe, Co, Ni, Cu, Mg, Ca, and Ba) shows distinct conformer patterns. These conformers appear to arise from individual metals binding at different sites on the glycan. Fragmentation studies suggest that these different binding sites influence the CID fragmentation patterns. This paper describes a series of separation, activation, and fragmentation studies that assess which fragments arise from each of the different gas-phase conformer states. Comparison of the glycan distributions formed under gentle ionization conditions with those obtained after activation of the gas-phase ions suggests that these conformer binding states also appear to exist in solution.

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Section: Methodsmentioning

confidence: 99%

Populations of Metal-Glycan Structures Influence MS Fragmentation Patterns

Zhu

Glover

Shi

et al. 2014

J. Am. Soc. Mass Spectrom.

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“…The IMS profiles of a series of glycopeptides varying only in the attached glycans allow evaluation of the structural diversity of glycan moieties associated with each peptide. The inclusion of an IMS-CID-MS [54–57] platform in this workflow provides a means of distinguishing and determining isomeric glycans from this glycoprotein.…”

Section: Introductionmentioning

confidence: 99%

Glycopeptide Site Heterogeneity and Structural Diversity Determined by Combined Lectin Affinity Chromatography/IMS/CID/MS Techniques

Zhu

Trinidad

Clemmer

2015

J. Am. Soc. Mass Spectrom.

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Glycopeptides from a tryptic digest of chicken ovomucoid were enriched using a simplified lectin affinity chromatography (LAC) platform, and characterized by high-resolution mass spectrometry (MS) as well as ion mobility spectrometry (IMS)-MS. The LAC platform effectively enriched the glycoproteome, from which a total of 117 glycopeptides containing 27 glycan forms were identified for this protein. IMS-MS analysis revealed a high degree of glycopeptide site heterogeneity. Comparing the IMS distributions of the glycopeptides from different charge states reveals that higher charge states allow more structures to be resolved. Presumably the repulsive interactions between charged sites lead to more open configurations which are more readily separated compared with the more compact, lower charge state forms of the same groups of species. Combining IMS with collision induced dissociation (CID) made it possible to determine the presence of isomeric glycans and to reconstruct their IMS profiles. This study illustrates a workflow involving hybrid techniques for determining glycopeptide site heterogeneity and evaluating structural diversity of glycans and glycopeptides.

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“…Preparing samples as methyl derivatives, detailed studies with known biologics, and numerous applications were convincing (19 -22), and the outgrowth of these and related studies was that glycan isomers have been universally overlooked, even in classic glycoprotein standards, RNase B and ovalbumin (23,24). In both examples, such findings have recently been confirmed by extensive orthogonal efforts using HPLC (25) and IMMS (26). Motivated by these earlier findings, we initiated a searchable library of fragments compiled from commercially available small oligomers (27), an ongoing effort supported now by major synthetic teams (see Acknowledgments).…”

Section: Sequence Documentation Itms N General Considerationsmentioning

confidence: 80%

Toward a Platform for Comprehensive Glycan Sequencing

Reinhold

Zhang

Hanneman

et al. 2013

Molecular & Cellular Proteomics

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From a series of recently published reports, an analytical platform has been proposed for a quantitative and qualitative measure of N-and O-glycosylation, complete with peptide-glycan connectivity and detailed structural understanding. As distant as this may appear, a best methods approach will appear that must move us beyond the cartoon stage of structural understanding. Thus, with this unifying goal in mind, we summarize a series of individually promising first phase protocols of sample preparation (release, purification, and quantification) that remain congruent with a concluding phase (methylation and MS n ) for documented structural detail. Sequential enzymatic Nglycan and chemical O-glycan release from glycopeptides with intervening solid phase extraction and derivatization will provide for a comparative quantification measure of glycosylation. The O-glycan release will be nonreductive and coupled with Michael addition to a pyrazolone analog (1-phenyl-3-methyl-5-pyrazolone) with both the peptide and glycan labeled. The product glycans are stable to methylation and appropriate for sequential disassembly (MS n ). An application using human serum and cancer samples has been detailed characterizing sLe x and comparable valence epitopes. This integrated platform will provide opportunities at variable points to contrast, share, and advance alternative protocols in a collaborative effort that is greatly needed. This integrated platform provides end point opportunities to confirm structural details compiled from synthetic standards and well characterized biologics by MS n . Molecular & Cellular Proteomics 12: 10.1074/mcp.R112.026823, 866 -873, 2013. A UNIFIED GLYCOMICS PLATFORMThe NHLBI, National Institutes of Health, established a Program of Excellence in Glycosciences that supports a study of glycans ubiquitously found on the surfaces of all mammalian cells. Such structures influence a wide variety of cellular and disease-related processes that are governed by the composition and configuration of the interacting partners and the details of structure and conformation within that supramolecular environment. An example of these cohorts are the selectins (E-, L-, and P-) that bind to sialofucosylated ligands displayed on their respective glycans (1, 2). Following an earlier focus by the NIGMS and the NCI of the National Institutes of Health, the NHLBI introduced this Program of Excellence in Glycosciences to bring a more comprehensive glycomics endeavor to support the growing importance of glycan structures in heart, lung, and blood disease research. The Program of Excellence has established three fundamental goals as follows: (i) to develop and expand core facilities across the country; (ii) to facilitate collaborations and distribute research findings, and (iii) to train future generations of scientists to be cognizant in both glycan biology and chemistry. These are laudable goals by any measure, but what blurs the effort and forward momentum must be the considerations of the last goal. With the expanding list of ...

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Mannose7 Glycan Isomer Characterization by IMS-MS/MS Analysis

Cited by 67 publications

References 47 publications

Populations of Metal-Glycan Structures Influence MS Fragmentation Patterns

Populations of Metal-Glycan Structures Influence MS Fragmentation Patterns

Glycopeptide Site Heterogeneity and Structural Diversity Determined by Combined Lectin Affinity Chromatography/IMS/CID/MS Techniques

Toward a Platform for Comprehensive Glycan Sequencing

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