Synthesis and antibiotic activities of CRAMP, a cathelin-related antimicrobial peptide and its fragments

CRAMP, a 37-amino acid cationic antimicrobial peptide was recently deduced from the cDNA cloned from mouse femoral marrow RNA. In order to investigate the structure-activity relationship and functional region of CRAMP, CRAMP and its Is-mer overlapping peptides were synthesized by the solid phase met hod. CRAMP showed broad spectrum antibacterial activity against both Gram-p ositive and Gram-negative bacterial strains (MIC: 3.125-6.25 mu M) but had no hemolytic activity until 50 mu M. CRAMP was found to have a potent antic ancer activity (IC50: 12-23 mu M) against two human small cell lung cancer cell lines. Furthermore, CRAMP was found to display faster bactericidal rat e in B. subtilis rather than E. coli in the kinetics of bacterial killing. Among 18-meric overlapping fragment peptides, only CRAMP (16-33) displayed potent antibacterial activity (MIC: 12.5-50 mu M) against several bacteria with no hemolytic activity. Circular dichroism (CD) spectra analysis indica ted that CRAMP and its analogues will form the amphipathic cw-helical confo rmation in the cell membranes similar to other antimicrobial peptides, such as cecropins and magainins.