Ion‐Mobility Spectrometry Can Assign Exact Fucosyl Positions in Glycans and Prevent Misinterpretation of Mass‐Spectrometry Data After Gas‐Phase Rearrangement

Toraño, Javier Sastre; Gagarinov, Ivan A.; Vos, Gaël M.; Broszeit, Frederik; Srivastava, Apoorva D.; Palmer, Martin; Langridge, James; Aizpurua‐Olaizola, Oier; Somovilla, Víctor J.; Boons, Geert‐Jan

doi:10.1002/anie.201909623

“…Protonated carbohydrates present additional challenges, as they can undergo rearrangement reactions, most notably migration of fucose during collision-induced dissociation (CID) 6 . This migration process is still under investigation [7][8][9] , and a general structural understanding of the even simple protonated carbohydrate systems is only now starting to emerge 10 . For intact glycoconjugates (i.e.…”

Section: Introductionmentioning

confidence: 99%

Linkage Memory in Underivatized Protonated Carbohydrates

Mookherjee¹,

Uppal²,

Murphree³

et al. 2020

Preprint

View full text Add to dashboard Cite

<p>Carbohydrates are among the most complex class of biomolecules and even subtle variations in their structures are attributed to diverse biological function. Mass spectrometry has been essential for large scale glycomics and glycoproteomics studies, but the gas-phase structures and sometimes anomalous fragmentation properties of carbohydrates present longstanding challenges. Here we investigate the gas-phase properties of a panel of isomeric protonated disaccharides differing in their linkage configurations. Multiple conformations were evident for most of the structures based on their fragment ion abundances by tandem mass spectrometry, their ion mobilities in several gases, and their deuterium uptake kinetics by gas-phase hydrogen deuterium exchange. Most notably, we find that the properties of the Y-ion fragments are characteristically influenced by the precursor carbohydrate’s linkage configuration. This study reveals how protonated carbohydrate fragment ions can retain ‘linkage memory’ that provides structural insight into their intact precursor.</p>

show abstract

“…Protonated carbohydrates present additional challenges, as they can undergo rearrangement reactions, most notably migration of fucose during collision-induced dissociation (CID) 6 . This migration process is still under investigation [7][8][9] , and a general structural understanding of the even simple protonated carbohydrate systems is only now starting to emerge 10 . For intact glycoconjugates (i.e.…”

Section: Introductionmentioning

confidence: 99%

Linkage Memory in Underivatized Protonated Carbohydrates

Mookherjee

¹

,

Uppal²,

Murphree³

et al. 2020

Preprint

0

View full text Add to dashboard Cite

<p>Carbohydrates are among the most complex class of biomolecules and even subtle variations in their structures are attributed to diverse biological function. Mass spectrometry has been essential for large scale glycomics and glycoproteomics studies, but the gas-phase structures and sometimes anomalous fragmentation properties of carbohydrates present longstanding challenges. Here we investigate the gas-phase properties of a panel of isomeric protonated disaccharides differing in their linkage configurations. Multiple conformations were evident for most of the structures based on their fragment ion abundances by tandem mass spectrometry, their ion mobilities in several gases, and their deuterium uptake kinetics by gas-phase hydrogen deuterium exchange. Most notably, we find that the properties of the Y-ion fragments are characteristically influenced by the precursor carbohydrate’s linkage configuration. This study reveals how protonated carbohydrate fragment ions can retain ‘linkage memory’ that provides structural insight into their intact precursor.</p>

show abstract

“…[31] Thus, it is now possible to prepares ufficiently large collections of compounds for IMS-MS data base development. Unknown N-glycans that are not incorporated in ad atabase, can be identified by MS/MS experiments in combination with IMS of fragment ions, [32] when synthesis of possible structure candidates is not an option. In addition, we developed an approacht oc ompute CCSDs for N-glycani dentification,a nd althoughr efinementsa re required, such an approach can also contributetodatabase development.…”

mentioning

confidence: 99%

Identification of Isomeric N‐Glycans by Conformer Distribution Fingerprinting using Ion Mobility Mass Spectrometry

Toraño

¹

,

Aizpurua‐Olaizola

²

,

Wei

³

et al. 2021

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

Glycans possess unparalleled structural complexity arising from chemically similar monosaccharide building blocks, configurations of anomeric linkages and different branching patterns, potentially giving rise to many isomers. This level of complexity is one of the main reasons that identification of exact glycan structures in biological samples still lags behind that of other biomolecules. Here, we introduce a methodology to identify isomeric N‐glycans by determining gas phase conformer distributions (CDs) by measuring arrival time distributions (ATDs) using drift‐tube ion mobility spectrometry‐mass spectrometry. Key to the approach is the use of a range of well‐defined synthetic glycans that made it possible to investigate conformer distributions in the gas phase of isomeric glycans in a systematic manner. In addition, we have computed CD fingerprints by molecular dynamics (MD) simulation, which compared well with experimentally determined CDs. It supports that ATDs resemble conformational populations in the gas phase and offer the prospect that such an approach can contribute to generating a library of CCS distributions (CCSDs) for structure identification.

show abstract

Ion‐Mobility Spectrometry Can Assign Exact Fucosyl Positions in Glycans and Prevent Misinterpretation of Mass‐Spectrometry Data After Gas‐Phase Rearrangement

Cited by 26 publications

References 35 publications

Linkage Memory in Underivatized Protonated Carbohydrates

Linkage Memory in Underivatized Protonated Carbohydrates

Linkage Memory in Underivatized Protonated Carbohydrates

Identification of Isomeric N‐Glycans by Conformer Distribution Fingerprinting using Ion Mobility Mass Spectrometry

Contact Info

Product

Resources

About