Design and Synthesis of Neutralizable Fondaparinux

Zhang，Liangwei1; Liu，Yating1,2; Xu，Zhuojia1,3; Hao，Tianhui1,3; Wang，Peng George4; Zhao，Wei5; Li，Tiehai1,2,3,6

2022

10.1021/jacsau.2c00537

Journal of the American Chemical Society   Impact Factor & Quartile

0002-7863

1520-5126

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.

anticoagulant agent glycosylation heparin oligosaccharide synthesis design

ESCI

English

NI Journal Papers

Others

National Natural Science Foundation of China[22077130] ; Science and Technology Commission of Shanghai Municipality[20ZR1467900]

Chemistry

Chemistry, Multidisciplinary

WOS:000885403400001

AMER CHEMICAL SOC

2-s2.0-85142120805

Scopus

1.Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China
2.School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing,210023,China
3.University of Chinese Academy of Sciences,Beijing,100049,China
4.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China
5.College of Pharmacy,Nankai University,Tianjin,300353,China
6.Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry,Sichuan University,Chengdu,610041,China

Zhang，Liangwei,Liu，Yating,Xu，Zhuojia,et al. Design and Synthesis of Neutralizable Fondaparinux[J]. Journal of the American Chemical Society,2022.

Zhang，Liangwei.,Liu，Yating.,Xu，Zhuojia.,Hao，Tianhui.,Wang，Peng George.,...&Li，Tiehai.(2022).Design and Synthesis of Neutralizable Fondaparinux.Journal of the American Chemical Society.

Zhang，Liangwei,et al."Design and Synthesis of Neutralizable Fondaparinux".Journal of the American Chemical Society (2022).