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Published January 2, 2023 | Supplemental Material + Published
Journal Article Open

Synthesis of a Systematic 64-Membered Heparan Sulfate Tetrasaccharide Library

Abstract

Heparan sulfate (HS) has multifaceted biological activities. To date, no libraries of HS oligosaccharides bearing systematically varied sulfation structures are available owing to the challenges in synthesizing a large number of HS oligosaccharides. To overcome the obstacles and expedite the synthesis, a divergent approach was designed, where 64 HS tetrasaccharides covering all possible structures of 2-O-, 6-O- and N-sulfation with the glucosamine-glucuronic acid-glucosamine-iduronic acid backbone were successfully produced from a single strategically protected tetrasaccharide intermediate. This extensive library helped identify the structural requirements for HS sequences to have strong fibroblast growth factor-2 binding but a weak affinity for platelet factor-4. Such a strategy to separate out these two interactions could lead to new HS-based potential therapeutics without the dangerous adverse effect of heparin-induced thrombocytopenia.

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) and Michigan State University for financial support of our work. Data Availability Statement. The data that support the findings of this study are available in the supplementary material of this article.

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Published - ANIE-62-0.pdf

Supplemental Material - ANIE-62-0-s001.pdf

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Additional details

Created:
August 22, 2023
Modified:
December 21, 2023