IMPROVED ACTIVITY OF A SYNTHETIC INDOLICIDIN ANALOG

A novel cationic peptide, CP-11, based on the structure of the bovine neutrophil peptide indolicidin, was designed to increase the number of positively charged residues, maintain the short length (13 amino acid s), and enhance the amphipathicity relative to those of indolicidin. C P-11, and especially its carboxymethylated derivative, CP-11C, demonst rated improved activity against gram-negative bacteria and Candida alb icans, while it maintained the activity of indolicidin against staphyl ococci and demonstrated a reduced ability to lyse erythrocytes, In Esc herichia coli, CP-11 was better able than indolicidin to permeabilize both the outer membrane, as indicated by the enhancement of uptake of 1-N-phenylnaphthylamine, and the inner membrane, as determined by the unmasking of cytoplasmic beta-galactosidase, providing an explanation for its improved activity.