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Chemistry and Biology of the Aeruginosin Family of Serine Protease Inhibitors

Authors

  • Karolina Ersmark Dr.,

    1. Department of Chemistry, Université de Montréal, C.P. 6128, Station Centre-ville, Montréal, PQ, H3C 3J7, Canada, Fax: (+1) 514-343-5728
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  • Juan R. Del Valle Dr.,

    1. Department of Chemistry and Biochemistry, New Mexico State University, 1175 North Horseshoe Drive MSC 3C, Las Cruces, NM 88003, USA
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  • Stephen Hanessian Prof.

    1. Department of Chemistry, Université de Montréal, C.P. 6128, Station Centre-ville, Montréal, PQ, H3C 3J7, Canada, Fax: (+1) 514-343-5728
    2. Department of Chemistry, University of Caifornia, Irvine, 516 Rowland Hall, Irvine, CA 92697-2025, USA
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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.

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