Effect of a chemical or proteolytic modification on the biological activity of guinea-pig cationic peptide.

Guinea-pig neutrophil cationic peptides (GNCPs) are single polypeptides containing 31 amino acid residues and three intramolecular disulfide bonds, which show both antibacterial and histamine-releasing activities. Reduction and alkylation of the disulfide bonds of GNCP did not reduce both biological activities. When pyridylethylated GNCP was digested with trypsin, the biological activities were almost lost, whereas the chymotryptic digest retained the biological activities. Chymotrypsin digested fragments were purified by RP-HPLC, and three active peptide fragments containing two Arg residues at the N-terminal sequence were isolated. When the biological activities were examined using synthetic peptides containing various numbers of Arg residue at the N-terminus, the omission of the Arg residues was found to reduce remarkably the antibacterial and histamine-releasing activities. Together these observations indicate that the primary structures containing Arg residues at the N-terminus but not the intramolecular disulfide cross-linking are important for the expression of the biological activities of GNCP.