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Review
Chemistry and Biology of the Aeruginosin Family of Serine Protease Inhibitors
Article first published online: 12 DEC 2007
DOI: 10.1002/anie.200605219
Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Ersmark, K., Del Valle, Juan R. and Hanessian, S. (2008), Chemistry and Biology of the Aeruginosin Family of Serine Protease Inhibitors. Angew. Chem. Int. Ed., 47: 1202–1223. doi: 10.1002/anie.200605219
Publication History
- Issue published online: 25 JAN 2008
- Article first published online: 12 DEC 2007
- Manuscript Received: 24 DEC 2006
Funded by
- NSERC
- AstraZeneca
- Abstract
- Article
- References
- Cited By
Keywords:
- inhibitors;
- natural products;
- octahydroindoles;
- peptides;
- thrombin
Abstract
The aeruginosins have been isolated from marine sponges and cyanobacterial waterblooms, sources that are phylogenetically distinct and the bodies of water are geographically well-separated. The aeruginosins comprise a central hydroxy- (or dihydroxy-) octahydroindole carboxamide core unit, onto which are appended unusual amino acids on the carboxy and amino termini as part of the linear peptide array. Potent inhibitory activity of serine proteases in vitro is exhibited by some of the aeruginosins as a result of the presence and proper deployment of three important pharmacophoric subunits: a P1 arginine mimetic, and two hydrophobic residues with interaction sites designated as P2 and P3. In this article, we provide the first comprehensive review on the chemistry and biology of the aeruginosins, with an emphasis on their sources, structural revisions, and total syntheses.