MODIFICATION OF A SYNTHETIC ANTIMICROBIAL PEPTIDE (ESF1) FOR IMPROVEDINHIBITORY ACTIVITY

Rational modification of an existing cationic ct-helical antimicrobial peptide (ESF1) for improved activity by increasing amphipathicity was undertaken. ESF1 and two variants (GR7 and SA3) were synthesized and tested for activity range, minimum inhibitory concentration, and hemol ytic activity. Biological activity was related to structure as determi ned by circular dichroism. The substitution of arginine for glycine in position seven was found to increase antimicrobial activity without e ffecting hemolysis. Increased activity was related to stronger alpha-h elix formation in buffer. Increased beta-sheet formation in micellar S DS was observed and speculated to be due to a stronger ability of the variants to form multimolecule complexes, a feature consistent with ex isting models of cationic peptide activity. (C) 1998 Academic Press.