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Heparan sulfate glycomimetics via iterative assembly of “clickable” disaccharides
Heparan sulfate (HS) glycosaminoglycans are widely expressed on the mammalian cell surfaces and extracellular matrices and play important roles in a variety of cell functions. Studies on the structure–activity relationships of HS have long been hampered by the challenges in obtaining chemically defi...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055906/ https://www.ncbi.nlm.nih.gov/pubmed/37006675 http://dx.doi.org/10.1039/d3sc00260h |
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author | Yang, Cangjie Deng, Yu Wang, Yang Xia, Chaoshuang Mehta, Akul Y. Baker, Kelly J. Samal, Anuj Booneimsri, Putthipong Lertmaneedang, Chanthakarn Hwang, Seung Flynn, James P. Cao, Muqing Liu, Chao Zhu, Alec C. Cummings, Richard D. Lin, Cheng Mohanty, Udayan Niu, Jia |
author_facet | Yang, Cangjie Deng, Yu Wang, Yang Xia, Chaoshuang Mehta, Akul Y. Baker, Kelly J. Samal, Anuj Booneimsri, Putthipong Lertmaneedang, Chanthakarn Hwang, Seung Flynn, James P. Cao, Muqing Liu, Chao Zhu, Alec C. Cummings, Richard D. Lin, Cheng Mohanty, Udayan Niu, Jia |
author_sort | Yang, Cangjie |
collection | PubMed |
description | Heparan sulfate (HS) glycosaminoglycans are widely expressed on the mammalian cell surfaces and extracellular matrices and play important roles in a variety of cell functions. Studies on the structure–activity relationships of HS have long been hampered by the challenges in obtaining chemically defined HS structures with unique sulfation patterns. Here, we report a new approach to HS glycomimetics based on iterative assembly of clickable disaccharide building blocks that mimic the disaccharide repeating units of native HS. Variably sulfated clickable disaccharides were facilely assembled into a library of mass spec-sequenceable HS-mimetic oligomers with defined sulfation patterns by solution-phase iterative syntheses. Microarray and surface plasmon resonance (SPR) binding assays corroborated molecular dynamics (MD) simulations and confirmed that these HS-mimetic oligomers bind protein fibroblast growth factor 2 (FGF2) in a sulfation-dependent manner consistent with that of the native HS. This work established a general approach to HS glycomimetics that can potentially serve as alternatives to native HS in both fundamental research and disease models. |
format | Online Article Text |
id | pubmed-10055906 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-100559062023-03-30 Heparan sulfate glycomimetics via iterative assembly of “clickable” disaccharides Yang, Cangjie Deng, Yu Wang, Yang Xia, Chaoshuang Mehta, Akul Y. Baker, Kelly J. Samal, Anuj Booneimsri, Putthipong Lertmaneedang, Chanthakarn Hwang, Seung Flynn, James P. Cao, Muqing Liu, Chao Zhu, Alec C. Cummings, Richard D. Lin, Cheng Mohanty, Udayan Niu, Jia Chem Sci Chemistry Heparan sulfate (HS) glycosaminoglycans are widely expressed on the mammalian cell surfaces and extracellular matrices and play important roles in a variety of cell functions. Studies on the structure–activity relationships of HS have long been hampered by the challenges in obtaining chemically defined HS structures with unique sulfation patterns. Here, we report a new approach to HS glycomimetics based on iterative assembly of clickable disaccharide building blocks that mimic the disaccharide repeating units of native HS. Variably sulfated clickable disaccharides were facilely assembled into a library of mass spec-sequenceable HS-mimetic oligomers with defined sulfation patterns by solution-phase iterative syntheses. Microarray and surface plasmon resonance (SPR) binding assays corroborated molecular dynamics (MD) simulations and confirmed that these HS-mimetic oligomers bind protein fibroblast growth factor 2 (FGF2) in a sulfation-dependent manner consistent with that of the native HS. This work established a general approach to HS glycomimetics that can potentially serve as alternatives to native HS in both fundamental research and disease models. The Royal Society of Chemistry 2023-02-28 /pmc/articles/PMC10055906/ /pubmed/37006675 http://dx.doi.org/10.1039/d3sc00260h Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Yang, Cangjie Deng, Yu Wang, Yang Xia, Chaoshuang Mehta, Akul Y. Baker, Kelly J. Samal, Anuj Booneimsri, Putthipong Lertmaneedang, Chanthakarn Hwang, Seung Flynn, James P. Cao, Muqing Liu, Chao Zhu, Alec C. Cummings, Richard D. Lin, Cheng Mohanty, Udayan Niu, Jia Heparan sulfate glycomimetics via iterative assembly of “clickable” disaccharides |
title | Heparan sulfate glycomimetics via iterative assembly of “clickable” disaccharides |
title_full | Heparan sulfate glycomimetics via iterative assembly of “clickable” disaccharides |
title_fullStr | Heparan sulfate glycomimetics via iterative assembly of “clickable” disaccharides |
title_full_unstemmed | Heparan sulfate glycomimetics via iterative assembly of “clickable” disaccharides |
title_short | Heparan sulfate glycomimetics via iterative assembly of “clickable” disaccharides |
title_sort | heparan sulfate glycomimetics via iterative assembly of “clickable” disaccharides |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055906/ https://www.ncbi.nlm.nih.gov/pubmed/37006675 http://dx.doi.org/10.1039/d3sc00260h |
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