Clavatadine A, a natural product with selective recognition and irreversible inhibition of factor XIa
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
Griffith University Author(s)
Year published
2008
Metadata
Show full item recordAbstract
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.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 Title
Journal of Medicinal Chemistry
Volume
51
Issue
12
Publisher URI
Copyright Statement
© 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.
Subject
Medicinal and biomolecular chemistry
Organic chemistry
Pharmacology and pharmaceutical sciences