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Design and Synthesis of Neutralizable Fondaparinux

[Image: see text] Fondaparinux, a clinically approved anticoagulant pentasaccharide for the treatment of thrombotic diseases, displays better efficacy and biosafety than other heparin-based anticoagulant drugs. However, there is no suitable antidote available for fondaparinux to efficiently manage i...

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Autores principales: Zhang, Liangwei, Liu, Yating, Xu, Zhuojia, Hao, Tianhui, Wang, Peng George, Zhao, Wei, Li, Tiehai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795572/
https://www.ncbi.nlm.nih.gov/pubmed/36590263
http://dx.doi.org/10.1021/jacsau.2c00537
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author Zhang, Liangwei
Liu, Yating
Xu, Zhuojia
Hao, Tianhui
Wang, Peng George
Zhao, Wei
Li, Tiehai
author_facet Zhang, Liangwei
Liu, Yating
Xu, Zhuojia
Hao, Tianhui
Wang, Peng George
Zhao, Wei
Li, Tiehai
author_sort Zhang, Liangwei
collection PubMed
description [Image: see text] Fondaparinux, a clinically approved anticoagulant pentasaccharide for the treatment of thrombotic diseases, displays better efficacy and biosafety than other heparin-based anticoagulant drugs. However, there is no suitable antidote available for fondaparinux to efficiently manage its potential bleeding risks, thereby precluding its widespread use. Herein, we describe a convergent and stereocontrolled approach to efficiently synthesize an aminopentyl-functionalized pentasaccharide, which is further used to prepare fondaparinux-based biotin conjugates and clusters. Biological activity evaluation demonstrates that the anticoagulant activity of the fondaparinux-based biotin conjugate and trimer is, respectively, neutralized by avidin and protamine as effective antidotes. This work suggests that our synthetic biotin conjugate and trimer have potential for the development of neutralizable and safe anticoagulant drugs.
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spelling pubmed-97955722022-12-29 Design and Synthesis of Neutralizable Fondaparinux Zhang, Liangwei Liu, Yating Xu, Zhuojia Hao, Tianhui Wang, Peng George Zhao, Wei Li, Tiehai JACS Au [Image: see text] Fondaparinux, a clinically approved anticoagulant pentasaccharide for the treatment of thrombotic diseases, displays better efficacy and biosafety than other heparin-based anticoagulant drugs. However, there is no suitable antidote available for fondaparinux to efficiently manage its potential bleeding risks, thereby precluding its widespread use. Herein, we describe a convergent and stereocontrolled approach to efficiently synthesize an aminopentyl-functionalized pentasaccharide, which is further used to prepare fondaparinux-based biotin conjugates and clusters. Biological activity evaluation demonstrates that the anticoagulant activity of the fondaparinux-based biotin conjugate and trimer is, respectively, neutralized by avidin and protamine as effective antidotes. This work suggests that our synthetic biotin conjugate and trimer have potential for the development of neutralizable and safe anticoagulant drugs. American Chemical Society 2022-11-14 /pmc/articles/PMC9795572/ /pubmed/36590263 http://dx.doi.org/10.1021/jacsau.2c00537 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Zhang, Liangwei
Liu, Yating
Xu, Zhuojia
Hao, Tianhui
Wang, Peng George
Zhao, Wei
Li, Tiehai
Design and Synthesis of Neutralizable Fondaparinux
title Design and Synthesis of Neutralizable Fondaparinux
title_full Design and Synthesis of Neutralizable Fondaparinux
title_fullStr Design and Synthesis of Neutralizable Fondaparinux
title_full_unstemmed Design and Synthesis of Neutralizable Fondaparinux
title_short Design and Synthesis of Neutralizable Fondaparinux
title_sort design and synthesis of neutralizable fondaparinux
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795572/
https://www.ncbi.nlm.nih.gov/pubmed/36590263
http://dx.doi.org/10.1021/jacsau.2c00537
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