PubMed1992
The location of amino acids in soluble or membrane proteins is related to the hydrophobicity of the side chains. Amino acid hydrophobicity values are based upon the thermodynamics of transfer from an aqueous to a nonaqueous environment. However, for certain hydrophilic residues uncertainty exists on the appropriate hydrophobicity values. We have measured the octanol-water partition coefficients (Po/w) of tripeptides of the sequence N-14C-acetyl-Ala-X-Ala-NH-tButyl (AcAlaXAlaNHtButyl), where the central residue X was either Gly, Ala, Phe, Trp, Pro, His, Asp, or Glu. The Po/w for the tripeptides agreed reasonably well with values calculated by the fragment method of D. J. Abraham and A. J. Leo (Proteins Struct. Func. Gen. 2, 130-152, 1987). The log Po/w of the uncharged form was 1.6, 2.7, and 2.5 greater than the log Po/w of the ionized form for the His, Asp, and Glu peptide, respectively. The new data on the pH dependence of the ionizable side chains, His, Asp, and Glu, should result in better prediction of the partition coefficient of peptides as a function of pH. The thermodynamic parameters were determined from the temperature dependence of partitioning. In the temperature range studied (2 to 65 degrees C) the transfer of tripeptides from water to octanol was entropy governed except for the ionized peptides. A heat capacity term was necessary to account for the transfer of tripeptides containing non polar residues. The heat capacity change for transfer from water into octanol was -45, -73, -81, and -88 cal/mol K for Ala, Phe, Trp, and Pro peptides, respectively. Peptides containing Gly, His (pH 7.2), and the uncharged forms of Asp, Glu, and His did not show a significant change in heat capacity. The side-chain contribution of the central residue X (delta Gx) to the free energy of transfer was obtained from the difference between the free energy of transfer of the peptide containing the central residue X and the Gly peptide; delta Gx = delta G(AcAlaXAlaNHtButyl) - delta G(AcAlaGlyAlaNHtButyl). The relative order of hydrophobicity of the side chains correlated well with previous studies. However, a significant difference was found for the absolute hydrophobicity between the present study and experimental data on N-acetyl amino acid amide derivatives (J. Fauchere and V. Pliska, Eur. J. Med. Chem. 18(4), 369-375, 1983).(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acids, Branched-Chain↗