Hydrophobic contribution constants of amino acid residues to the hydrophobicities of oligopeptides.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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).
Gao
H
H
Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles 90033, USA.
Wang
F
F
Lien
E J
EJ
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004151:Dipeptides / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*; D013678:Technology, Pharmaceutical; D014867:Water / Q000737:chemistry
D000596:Amino Acids; D004151:Dipeptides; D009842:Oligopeptides; D014867:Water