Quantitative analyses of hydrophobicity of di- to pentapeptides having un-ionizable side chains with substituent and structural parameters.

With experimental conditions established recently, we measured the partition ratio (P') of 124 di- to pentapeptides composed of amino acids having un-ionizable side chains in a 1-octanol:pH 7.0 aqueous phosphate buffer system as an approximate zwitterionized "molecular" partition coefficient (P). Empirical equations of good quality, correlating the variations in log P' value of peptides with free energy-related physicochemical parameters for the side chain substituents and substructures, were formulated. The significant side chain parameters were those representing the intrinsic hydrophobicity, the steric effect on the relative solvation of functional groups on the backbone, and the conformational potential index derived from the Chou-Fasman beta-turn potential parameters. For polar side chains, specific indicator variables were required for intramolecular hydrogen-bond formations and the "polar proximity effect" for reductions of hydrophilicity observed when polar groups are crowded together. The proline residue was shown to contribute to the log P' value depending not only on its location on the backbone but also on the number of residues in peptides. On the basis of the analyses, we proposed a new "effective" hydrophobicity index for un-ionizable side chains which could predict the secondary structure of oligopeptides.