Quantitative Structure-Hydrophobicity and Structure-Activity Relationships of Antibacterial Gramicidin S Analogs

Abstract

The structure–hydrophobicity–antibacterial activity relationships of gramicidin S and its analogs retaining a β-pleated sheet structure were examined quantitatively with physicochemical substituent and molecular parameters using regression analyses. Variations in their apparent hydrophobicity in an octanol/buffer (pH 7) system, logP(O/W), were analyzed in terms of the “effective” hydrophobicity and steric parameters of side chain substituents of residues at certain positions in the molecule; however, some of the conformational factors have not been fully defined. For the partitioning into liposomes and the growth inhibitory activity against species of Gram-positive bacteria, the logP(O/W) value simulated the hydrophobic effects of gramicidin S and its analogs better than substituent parameters. The side chain hydrophobicity was assumed to work together with effects attributed to variations in the entire cyclic peptide structure including conformational components undefined in the structure–logP(O/W) analysis in these activities.