Chemistry and biology of the aeruginosin family of serine protease inhibitors.
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.
Ersmark
Karolina
K
Department of Chemistry, Université de Montréal, C.P. 6128, Station Centre-ville, Montréal, PQ, H3C 3J7, Canada.
Del Valle
Juan R
JR
Hanessian
Stephen
S
D001896:Boron Compounds / Q000737:chemistry; D002384:Catalysis; D004583:Electrons; D005453:Fluorescence; D006863:Hydrogen-Ion Concentration; D008670:Metals / Q000737:chemistry; D015394:Molecular Structure; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000737:chemistry; D013057:Spectrum Analysis
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D008670:Metals; D015842:Serine Proteinase Inhibitors; D026082:Singlet Oxygen