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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
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.
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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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