Hydrophobicity of Peptides Containing D‐Amino Acids

Abstract

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/H(2)O 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 alpha A-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 (alpha or beta) to their C-terminal amino acid residues.