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Synthesis of a Systematic 64‐Membered Heparan Sulfate Tetrasaccharide Library

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 synthes...

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Autores principales: Baryal, Kedar N., Ramadan, Sherif, Su, Guowei, Huo, Changxin, Zhao, Yuetao, Liu, Jian, Hsieh‐Wilson, Linda C., Huang, Xuefei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933061/
https://www.ncbi.nlm.nih.gov/pubmed/36173931
http://dx.doi.org/10.1002/anie.202211985
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author Baryal, Kedar N.
Ramadan, Sherif
Su, Guowei
Huo, Changxin
Zhao, Yuetao
Liu, Jian
Hsieh‐Wilson, Linda C.
Huang, Xuefei
author_facet Baryal, Kedar N.
Ramadan, Sherif
Su, Guowei
Huo, Changxin
Zhao, Yuetao
Liu, Jian
Hsieh‐Wilson, Linda C.
Huang, Xuefei
author_sort Baryal, Kedar N.
collection PubMed
description 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.
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spelling pubmed-99330612023-04-18 Synthesis of a Systematic 64‐Membered Heparan Sulfate Tetrasaccharide Library Baryal, Kedar N. Ramadan, Sherif Su, Guowei Huo, Changxin Zhao, Yuetao Liu, Jian Hsieh‐Wilson, Linda C. Huang, Xuefei Angew Chem Int Ed Engl Research Articles 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. John Wiley and Sons Inc. 2022-12-01 2023-01-02 /pmc/articles/PMC9933061/ /pubmed/36173931 http://dx.doi.org/10.1002/anie.202211985 Text en © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Baryal, Kedar N.
Ramadan, Sherif
Su, Guowei
Huo, Changxin
Zhao, Yuetao
Liu, Jian
Hsieh‐Wilson, Linda C.
Huang, Xuefei
Synthesis of a Systematic 64‐Membered Heparan Sulfate Tetrasaccharide Library
title Synthesis of a Systematic 64‐Membered Heparan Sulfate Tetrasaccharide Library
title_full Synthesis of a Systematic 64‐Membered Heparan Sulfate Tetrasaccharide Library
title_fullStr Synthesis of a Systematic 64‐Membered Heparan Sulfate Tetrasaccharide Library
title_full_unstemmed Synthesis of a Systematic 64‐Membered Heparan Sulfate Tetrasaccharide Library
title_short Synthesis of a Systematic 64‐Membered Heparan Sulfate Tetrasaccharide Library
title_sort synthesis of a systematic 64‐membered heparan sulfate tetrasaccharide library
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933061/
https://www.ncbi.nlm.nih.gov/pubmed/36173931
http://dx.doi.org/10.1002/anie.202211985
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