Gao H, Wang F, Lien E J
Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles 90033, USA.
Pharm Res. 1995 Sep;12(9):1279-83. doi: 10.1023/a:1016257220102.
The main purpose of this study is to explore the additive-constitutive nature of common amino acids in their contribution to the partition coefficients of small peptides.
The Log P values and other physico-chemical parameters of the peptides studied are taken from the literature. The frequency of appearance (ni) of each individual amino acid is calculated as the number of the amino acids in a given peptide.
The partition coefficients (Log P(oct./buff.) at pH 7) of 87 N-acetyl-peptide-amides have been correlated with the frequency of appearance of amino acids. From the correlation obtained, the de novo hydrophobic contribution constants of 19 amino acid residues are derived for the first time. The contribution constants are extended to 59 unmodified regular peptides with the inclusion of the pka values of both N-terminal and C-terminal amino acids. The models thus obtained have been validated with additional 27 peptides (both N-acetyl-peptide-amides and unmodified).
The Log P of oligopeptides is very well correlated with the de novo hydrophobic contribution constants of amino acids. The models we have derived are reasonably accurate in predicting the hydrophobicities of new oligopeptides (< or = tetrapeptides) at a fixed pH (e.g., 7).
