Hydrophobicity of Peptides Containing D-Amino Acids

Several types of L-amino acid residues (Ser, Asp) in proteins are sometimes converted to D-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 containing D-amino acid residues, which may be generated by posttranslational isomerization (racemization or epimerization), to clarify the relationship between normal peptide residues composed of L-amino acids and the peptides containing D-amino acid residues. Calculated log P (log P_calc, where P is 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 (log P_exp) reported in the literatures. A linear correlation was found between log P_calc and log P_exp except for basic and aromatic amino acids, and peptides. Calculations on homo-oligopeptide diastereoisomers composed of alanine, valine, leucine, and aspartic acid showed differences in log P_calc values between diastereoisomers. Pentapeptides containing Asp residues that are most racemized or even inverted in αA-crystallin were also calculated to show that log P_calc values of pentapeptides differ depending on the configuration (D or L) and kinds of linkage (α or β) to their C-terminal amino acid residues.