Clavatadine A, A Natural Product with Selective Recognition and Irreversible Inhibition of Factor XIa
| Autor: | Yunjiang Feng, Thomas Fex, Linda Öster, Anthony R. Carroll, Malcolm Stewart Buchanan, Ronald J. Quinn, Yafeng Xue, Vicky M. Avery, Michael F. Jobling, Johanna Deinum, Rohan A. Davis, Deborah Wessling, John N. A. Hooper |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy medicine.drug_mechanism_of_action Stereochemistry Factor Xa Inhibitor Chemical Fractionation Crystallography X-Ray Guanidines chemistry.chemical_compound Fibrinolytic Agents Drug Discovery Antithrombotic medicine Animals IC50 Phenylacetates chemistry.chemical_classification Serine protease Biological Products Natural product Molecular Structure biology Hydrogen Bonding Biological activity Porifera Enzyme chemistry Factor Xa biology.protein Molecular Medicine Fibrinolytic agent Factor Xa Inhibitors |
| Zdroj: | Journal of Medicinal Chemistry. 51:3583-3587 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm800314b |
| Popis: | 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 microM, 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. |
| Databáze: | OpenAIRE |
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