Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides
| Autor: | Jeremy E. Turnbull, Rebecca L. Miller, Kevin Pagel, Johanna Hofmann, Scott E. Guimond, Jian Liu, Yongmei Xu, Olga V. Zubkova, Márkó Grabarics, Weston B. Struwe, Peter C. Tyler, Christian Manz, Niclas G. Karlsson, Geert-Jan Boons, Pradeep Chopra, Ralf Schwörer |
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| Přispěvatelé: | Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
carbohydrates General Physics and Astronomy Oligosaccharides Shotgun Glucuronic Acid/chemistry Sequence Analysis/methods Fibroblast growth factor 01 natural sciences chemistry.chemical_compound Epitopes Glucuronic Acid Heparitin Sulfate/chemistry lcsh:Science mass spectrometry chemistry.chemical_classification Multidisciplinary Heparan sulfate Oligosaccharide 3. Good health Biochemistry 500 Naturwissenschaften und Mathematik::540 Chemie::547 Organische Chemie Sulfotransferases Sequence Analysis Ion-mobility spectrometry Sequence analysis Science Oligosaccharides/chemistry 010402 general chemistry Mass spectrometry General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Structure-Activity Relationship glycobiology Structure–activity relationship Mass Spectrometry/methods Ions Heparin Fibroblast Growth Factors/metabolism General Chemistry R1 0104 chemical sciences Fibroblast Growth Factors 030104 developmental biology chemistry lcsh:Q Heparitin Sulfate Sulfotransferases/metabolism |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020) Nature Communications Nature Communications, 11(1). Nature Publishing Group Nature communications 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, vol. 11, no. 1, 1481 . https://doi.org/10.1038/s41467-020-15284-y |
| ISSN: | 2041-1723 |
| Popis: | 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. Heparan sulfates (HS) contain functionally relevant structural motifs, but determining their monosaccharide sequence remains challenging. Here, the authors develop an ion mobility mass spectrometry-based method that allows unambiguous characterization of HS sequences and structure-activity relationships. |
| Databáze: | OpenAIRE |
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