Comprehensive synthesis and anticoagulant evaluation of a diverse fucoidan library

Si-Cong Chen, Xianjin Qin, Nanyu Xiong, Lisha Lin, Yanfen Wu, Qin Li, Dongyue Sun, Xiong De-Cai, Cassandra E. Callmann, Mingyi Wu () and Xin-Shan Ye ()
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Si-Cong Chen: Peking University
Xianjin Qin: Peking University
Nanyu Xiong: Chinese Academy of Sciences
Lisha Lin: Chinese Academy of Sciences
Yanfen Wu: Peking University
Qin Li: Peking University
Dongyue Sun: Peking University
Xiong De-Cai: Peking University
Cassandra E. Callmann: The University of Texas at Austin
Mingyi Wu: Chinese Academy of Sciences
Xin-Shan Ye: Peking University

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract Fucoidan, a sulfated glycan derived from brown algae, has garnered significant attention for its anticoagulant properties. However, the structural complexity and heterogeneity of naturally extracted fucoidan have hindered a comprehensive understanding of its structure-activity relationship, limiting the development of fucoidan-based anticoagulant drugs. To address this challenge, we synthesize a diverse library of 58 distinct fucoidans with multiple contiguous 1,2-cis glycosidic bonds, ranging from disaccharides to dodecasaccharides, using a highly efficient preactivation-based one-pot glycosylation strategy. This library includes compounds with various sulfation patterns (2,3-O-di-, 3,4-O-di-, and 2,3,4-O-tri-sulfation) encompassing nearly all possible fucoidan structures. In vitro anticoagulant assays demonstrate that both molecular size and degree of sulfation play crucial roles in anticoagulant potency. Notably, compounds 29, 30, 37, and 58 significantly prolong human plasma activated partial thromboplastin time (APTT), comparable to the effect of enoxaparin, without affecting prothrombin time (PT) or thrombin time (TT). This selective inhibition of the intrinsic coagulation pathway suggests a reduced risk of bleeding, highlighting the therapeutic potential of these fucoidans as safer anticoagulant agents.

Date: 2025
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DOI: 10.1038/s41467-025-59632-2

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