Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1784889594348568576 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9933061 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT baryalkedarn synthesisofasystematic64memberedheparansulfatetetrasaccharidelibrary AT ramadansherif synthesisofasystematic64memberedheparansulfatetetrasaccharidelibrary AT suguowei synthesisofasystematic64memberedheparansulfatetetrasaccharidelibrary AT huochangxin synthesisofasystematic64memberedheparansulfatetetrasaccharidelibrary AT zhaoyuetao synthesisofasystematic64memberedheparansulfatetetrasaccharidelibrary AT liujian synthesisofasystematic64memberedheparansulfatetetrasaccharidelibrary AT hsiehwilsonlindac synthesisofasystematic64memberedheparansulfatetetrasaccharidelibrary AT huangxuefei synthesisofasystematic64memberedheparansulfatetetrasaccharidelibrary |