Clavatadine A, a natural product with selective recognition and irreversible inhibition of factor XIa

被引：60

作者：

Buchanan, Malcolm S. ^{[1
]}

Carroll, Anthony R. ^{[1
]}

Wessling, Deborah ^{[1
]}

Jobling, Michael ^{[1
]}

Avery, Vicky M. ^{[1
]}

Davis, Rohan A. ^{[1
]}

Feng, Yunjiang ^{[1
]}

Xue, Yafeng ^{[2
]}

Oster, Linda ^{[2
]}

Fex, Tomas ^{[2
]}

Deinum, Johanna ^{[2
]}

Hooper, John N. A. ^{[3
]}

Quinn, Ronald J. ^{[1
]}

机构：

[1] Griffith Univ, Eskitis Inst, Brisbane, Qld 4111, Australia

[2] AstraZeneca R&D, Molndal, Sweden

[3] Queensland Ctr Biodivers, Queensland Museum, Brisbane, Qld 4101, Australia

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 12期

关键词：

D O I：

10.1021/jm800314b

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Bioassay-guided fractionation of a CH(2)Cl(2)/MeOH extract of the sponge Suberea clavata using the serine protease factor XIa to detect antithrombotic activity led to the isolation of the new marine natural products, clavatadines A and B. Clavatadines A and B inhibited factor XIa with IC(50)'s of 1.3 and 27 mu M, respectively. A crystal structure of protein-inhibitor (clavatadine A) complex was obtained and revealed interesting selective binding and irreversible inhibition of factor XIa. The cocrystal structure provides guidance for the design and synthesis of future factor XIa inhibitors as antithrombotic agents.

引用

页码：3583 / 3587

页数：5

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