Expedient Synthesis of a Library of Heparan Sulfate‐Like "Head-to-Tail" Linked Multimers for Structure and Activity Relationship Studies
Creators
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1.
Michigan State University
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2.
Rensselaer Polytechnic Institute
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3.
Benha University
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4.
University of North Carolina at Chapel Hill
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5.
California Institute of Technology
Abstract
Heparan sulfate (HS) plays important roles in many biological processes. The inherent complexity of naturally existing HS has severely hindered the thorough understanding of their structure-activity relationship. To facilitate biological studies, a new strategy has been developed to synthesize a HS-like pseudo-hexasaccharide library, where HS disaccharides were linked in a "head-to-tail" fashion from the reducing end of a disaccharide module to the non-reducing end of a neighboring module. Combinatorial syntheses of 27 HS-like pseudo-hexasaccharides were achieved. This new class of compounds bound with fibroblast growth factor 2 (FGF-2) with similar structure-activity trends as HS oligosaccharides bearing native glycosyl linkages. The ease of synthesis and the ability to mirror natural HS activity trends suggest that the new head-to-tail linked pseudo-oligosaccharides could be an exciting tool to facilitate the understanding of HS biology.
Additional Information
© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. We are grateful for financial supports from the National Institute of General Medical Sciences, NIH (R01GM072667, U01GM116262, and R44GM134738 to X.H., J.L. and L.H.; S10OD028523 to F.Z. and R.L.), National Institute of Environmental Health Sciences (R01ES030695 to J.J.B.), the National Science Foundation (DMR-1933525 to F.Z., J.L. and R.L.), and Michigan State University for financial support of our work. We would like to thank Prof. Erika Lisabeth (Assay Development and Drug Discovery Core, MSU) for her expert help on SPR data processing. Data Availability Statement. The data that support the findings of this study are available in the Supporting Information of this article. Conflict of interest. J.L. is a founder and chief scientific officer for Glycan Therapeutics. He has equity in the company and serves as a paid consultant.Attached Files
Published - ANIE-61-0.pdf
Supplemental Material - ANIE-61-0-s001.pdf
Files
ANIE-61-0-s001.pdf
Additional details
Identifiers
- PMCID
- PMC9675719
- Eprint ID
- 117756
- Resolver ID
- CaltechAUTHORS:20221107-999291600.29
Funding
- NIH
- R01GM072667
- NIH
- U01GM116262
- NIH
- R44GM134738
- NIH
- S10OD028523
- NIH
- R01ES030695
- NSF
- DMR-1933525
- Michigan State University
Dates
- Created
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2022-11-18Created from EPrint's datestamp field
- Updated
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2023-07-06Created from EPrint's last_modified field