STRUCTURAL AND CHARGE REQUIREMENTS FOR ANTIMICROBIAL AND HEMOLYTIC-ACTIVITY IN THE PEPTIDE PKLLETFLSKWIG, CORRESPONDING TO THE HYDROPHOBIC REGION OF THE ANTIMICROBIAL PROTEIN BOVINE SEMINALPLASMIN

Several analogs of the 13-residue antimicrobial and hemolytic peptide PKLLETFLSKWIG (SPF), which is the most hydrophobic region of the 47-re sidue antimicrobial protein seminalplasmin [Sitaram, N. & Nagaraj, R. (1990) J. Biol. Chem. 265, 10438-10442] have been synthesized. The ant imicrobial and hemolytic properties of the peptides were investigated with a view to gain an insight into the structural and charge requirem ents for these activities of SPF. Peptides in which E was replaced by K exhibited considerably improved antimicrobial activity with no conco mitant increase in hemolytic activity. A peptide in which the aromatic amino acids were replaced by leucine exhibited antimicrobial activity like those of the peptides which had aromatic amino acids. Interchang e in the positions of E and K and total replacement of K by E resulted in complete loss of activity. The peptides having antimicrobial activ ities showed appreciable helical content in a hydrophobic environment, whereas inactive peptides did not. Thus, by suitable 'engineering' th e biological activity of a short 13-residue peptide can be altered to yield peptides specifically having only antimicrobial activity with in creased potency. (C) Munksgaard 1995.