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Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides

journal contribution
posted on 2021-02-01, 20:50 authored by RL Miller, SE Guimond, Ralf SchwoererRalf Schwoerer, Olga ZubkovaOlga Zubkova, Peter TylerPeter Tyler, Y Xu, J Liu, P Chopra, GJ Boons, M Grabarics, C Manz, J Hofmann, NG Karlsson, JE Turnbull, WB Struwe, K Pagel
© 2020, The Author(s). Despite evident regulatory roles of heparan sulfate (HS) saccharides in numerous biological processes, definitive information on the bioactive sequences of these polymers is lacking, with only a handful of natural structures sequenced to date. Here, we develop a “Shotgun” Ion Mobility Mass Spectrometry Sequencing (SIMMS2) method in which intact HS saccharides are dissociated in an ion mobility mass spectrometer and collision cross section values of fragments measured. Matching of data for intact and fragment ions against known values for 36 fully defined HS saccharide structures (from di- to decasaccharides) permits unambiguous sequence determination of validated standards and unknown natural saccharides, notably including variants with 3O-sulfate groups. SIMMS2 analysis of two fibroblast growth factor-inhibiting hexasaccharides identified from a HS oligosaccharide library screen demonstrates that the approach allows elucidation of structure-activity relationships. SIMMS2 thus overcomes the bottleneck for decoding the informational content of functional HS motifs which is crucial for their future biomedical exploitation.

History

Preferred citation

Miller, R. L., Guimond, S. E., Schwörer, R., Zubkova, O. V., Tyler, P. C., Xu, Y., Liu, J., Chopra, P., Boons, G. J., Grabarics, M., Manz, C., Hofmann, J., Karlsson, N. G., Turnbull, J. E., Struwe, W. B. & Pagel, K. (2020). Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides. Nature Communications, 11(1), 1481-. https://doi.org/10.1038/s41467-020-15284-y

Journal title

Nature Communications

Volume

11

Issue

1

Publication date

2020-12-01

Pagination

1481

Publisher

Springer Science and Business Media LLC

Publication status

Published

Online publication date

2020-03-20

ISSN

2041-1723

eISSN

2041-1723

Article number

1481

Language

en