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Shotgun ion mobilit...
Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides
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Miller, R. L. (author)
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Guimond, S. E. (author)
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Schworer, R. (author)
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Zubkova, O. V. (author)
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Tyler, P. C. (author)
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Xu, Y. M. (author)
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Liu, J. (author)
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Chopra, P. (author)
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Boons, G. J. (author)
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Grabarics, M. (author)
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Manz, C. (author)
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Hofmann, J. (author)
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- Karlsson, Niclas G., 1966 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine
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Turnbull, J. E. (author)
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Struwe, W. B. (author)
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Pagel, K. (author)
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(creator_code:org_t)
- 2020-03-20
- 2020
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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https://www.nature.c...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
Keyword
- electron detachment dissociation
- collision cross-sections
- glycosaminoglycan tetrasaccharides
- chemoenzymatic synthesis
- high-throughput
- iduronic acid
- oligosaccharides
- identification
- separation
- conformation
- Science & Technology - Other Topics
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Miller, R. L.
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Guimond, S. E.
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Schworer, R.
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Zubkova, O. V.
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Tyler, P. C.
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Xu, Y. M.
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show more...
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Liu, J.
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Chopra, P.
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Boons, G. J.
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Grabarics, M.
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Manz, C.
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Hofmann, J.
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Karlsson, Niclas ...
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Turnbull, J. E.
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Struwe, W. B.
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Pagel, K.
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Structural Biolo ...
- Articles in the publication
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Nature Communica ...
- By the university
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University of Gothenburg