Abstract
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 acids), and enhance the amphipathicity relative to those of indolicidin. CP-11, and especially its carboxymethylated derivative, CP-11C, demonstrated improved activity against gram-negative bacteria and Candida albicans, while it maintained the activity of indolicidin against staphylococci and demonstrated a reduced ability to lyse erythrocytes. In Escherichia 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.