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

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Author(s)
Buchanan, Malcolm S
Carroll, Anthony R
Wessling, Deborah
Jobling, Michael
Avery, Vicky M
Davis, Rohan A
Feng, Yunjiang
Xue, Yafeng
Oster, Linda
Fex, Tomas
Deinum, Johanna
Hooper, John NA
Quinn, Ronald J
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Dr. Philip S Portoghese (Editor-in-Chief), Laurence H Hurley (Senior Editor), Yusuf J Abul-Hajj (Sen

Date
2008
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Abstract

Bioassay-guided fractionation of a CH2Cl2/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 IC50's of 1.3 and 27 卬 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.

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Journal of Medicinal Chemistry

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51

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12

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© 2008 American Chemical Society. Self-archiving of the author-manuscript version is not yet supported by this publisher. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.

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Medicinal and biomolecular chemistry

Organic chemistry

Pharmacology and pharmaceutical sciences

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