Hydrophobicity of Peptides ContainingD‐Amino Acids

AbstractSeveral types ofL‐amino acid residues (Ser, Asp) in proteins are sometimes converted toD‐amino acid residues by posttranslational isomerization. This phenomenon leads to an increase in hydrophobicity and results in their deposition from aqueous media. This research involves the hydrophobicity of oligopeptides containingD‐amino acid residues, which may be generated by posttranslational isomerization (racemization or epimerization), to clarify the relationship between normal peptide residues composed ofL‐amino acids and the peptides containingD‐amino acid residues. Calculated logP(logPcalc, wherePis the octan‐1‐ol/H2O partition coefficient) values for many amino acids and oligopeptide diastereoisomers have been obtained by a semiempirical calculation method based on the PM5 Hamiltonian and compared with the experimental values (logPexp) reported in the literatures. A linear correlation was found between logPcalcand logPexpexcept for basic and aromatic amino acids, and peptides. Calculations on homo‐oligopeptide diastereoisomers composed of alanine, valine, leucine, and aspartic acid showed differences in logPcalcvalues between diastereoisomers. Pentapeptides containing Asp residues that are most racemized or even inverted inαA‐crystallin were also calculated to show that logPcalcvalues of pentapeptides differ depending on the configuration (DorL) and kinds of linkage (αorβ) to their C‐terminal amino acid residues.