Effects of D-Lysine Substitutions on the Activity and Selectivity of Antimicrobial Peptide CM15.

Despite their potent antimicrobial activity, the usefulness of antimicrobial peptides (AMPs) as antibiotics has been limited by their toxicity to eukaryotic cells and a lack of stability . In the present study we examined the effects of introducing D-lysine residues into a 15-residue hybrid AMP containing residues 1-7 of cecropin A and residues 2-9 of melittin (designated CM15). Diastereomeric analogs of CM15 containing between two and five D-lysine substitutions were evaluated for their antimicrobial activity, lysis of human erythrocytes, toxicity to murine macrophages, ability to disrupt cell membranes, and protease stability.