CRAMP analog having potent antibiotic activity without hemolytic activity

CRAMP-18 is an 18-residue functional region, corresponding to residues 16-33 of a mouse-derived Antibiotic peptide CRAMP. To develop novel Antibiotic peptides possessing strong Antibiotic activity against Bacterial, Fungal and tumor cells without hemolytic activity, three analogs of CRAMP-18 were synthesized containing either Leu- or Lys-substitution. Leu-substitution ([L(1, 8)]-CRAMP-18) in the hydrophobic helix face of CRAMP-18 induced a dramatic increase in Antibiotic activity without a significant increase in hemolytic activity. Lys-substitution ([K(2, 13)]-CRAMP-18 or [K(9, 16)]-CRAMP-18) in the hydrophilic helix face produced a smaller response. Therefore, [L(1, 8)]-CRAMP-18 may be an attractive candidate for developing novel peptide Antibiotics.