SYNTHETIC BACTERICIDAL PEPTIDE-BASED ON CAP37 - A 37-KDA HUMAN NEUTROPHIL GRANULE-ASSOCIATED CATIONIC ANTIMICROBIAL PROTEIN CHEMOTACTIC FORMONOCYTES

CAP37 (cationic antimicrobial protein of molecular mass 37 kDa) is a m ultifunctional protein isolated from the granules of human neutrophils . It is antibiotic and chemotactic and binds lipopolysaccharide. A syn thetic peptide, amino acid sequence NQGRHFCGGALIHARFVMTAASCFQ, based o n residues 20-44 of CAP37 protein mimics its antibiotic and lipopolysa ccharide binding action. Peptide 20-44, at the concentrations tested, has antibacterial activity against Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecalis, and Staphylococc us aureus. The bactericidal action of the peptide was pH dependent, wi th maximum activity at pH 5.0 and pH 5.5 and decreased activity at pH 7.0. Various truncations, substitutions, and other modifications in th e sequence deteriorate its activity. Free sulfhydryl groups and/or dis ulfide bridge formation are required for optimum antibiotic activity, since substitution of serines for, or alkylation of, cysteine residues 26 and 42 eliminates bactericidal activity. Evidently amino acids 20- 44 represent an important, perhaps principal, antibacterial domain of CAP37. This peptide should provide new insight into the mechanism of a ntimicrobial activity of CAP37 and may serve as a model for new, usefu l, synthetic antibiotics.