EFFECT OF A HYDROPHOBIC AMINO-ACID AT POSITION (I-1) ON THE STABILITYOF BETA-TURNS IN HYDROPHILIC PENTAPEPTIDES AS STUDIED BY NMR AND MOLECULAR MECHANICS

A detailed NMR study of the peptide NAc-FDEKA-NH2 in aqueous and in CD 3OH/H2O solutions as well as the N-acetylpentapeptide amides YDEKA, VD EKA, GDEKA, and the protected tetrapeptide NAc-DEKA-NH2 in methanolic solutions indicates the importance of the first amino acid (at i - 1) on stabilizing the type I beta-turn. The data illustrate the hydrophob ic stabilization of this turn, which is present in FDEKA, YDEKA, and V DEKA. For GDEKA and DEKA, the NMR data indicate that this turn is not present. Molecular mechanics calculations support this conclusion and indicate that for FDEKA and GDEKA the type I beta-turn is distorted in both the vacuum and the solvated structures. For the solvated structu res, the C-alpha(i)-C-alpha(i + 3) distance is 4.87 Angstrom for FDEKA and 6.00 Angstrom for GDEKA, which are to be compared with the value of 4.64 Angstrom for an ideal type I beta-turn, i.e., the distortion i s far greater in GDEKA than in FDEKA. The calculations can be interpre ted to indicate the presence of two major conformations in solution.