Antibacterial and hemolytic activities of single tryptophan analogs of indolicidin

The structure and biological activities of analogs of the bovine neutrophil antibacterial and hemolytic peptide indolicidin, ILPWKWPWWPWRR-amide, wher e one tryptophan at 4th, 8th, or 11th position has been retained and the ot hers replaced by leucine, have been investigated. All the single tryptophan analogs exhibit antibacterial activity. However, unlike indolicidin, they do not lyse erythrocytes. Structure analysis by circular dichroism spectros copy indicates that the analogs are unordered in aqueous medium and adopt p -turn structures in trifluoroethanol and micelles. The tryptophan residues in indolicidin appear to be essential for hemolytic activity but not antiba cterial activity. The nonspecific biological activities of indolicidin and specific antibacterial activity of single tryptophan analogs suggest that i n short peptides, a moth composed of hydrophobic amino acids with the excep tion of tryptophan, interspaced with proline residues and cationic amino ac ids at the N or C termini would favor selective antibacterial activity. (C) 2000 Academic Press.