PEPTIDES CONSTRAINED TO TYPE-VI BETA-TURNS .1. EVIDENCE FOR AN EXCEPTIONALLY STABLE INTRAMOLECULAR HYDROGEN-BOND

The synthesis and conformational analysis of conjugates of amino acids with a type VI beta-turn dipeptide mimic (1) is described. The mimic possessed high structural similarity to the central two residues of th e turn and was constrained from rotation about two of the four single bonds. Coupling of amino acids to the carboxyl group of the mimic affo rded conjugates that were capable of forming intramolecular hydrogen b onds. In nonpolar solvents, IR and NMR spectra of the conjugates indic ated that the amide hydrogen of the amino acid residue was hydrogen bo nded to the carbonyl group of the N-terminal carbamate functionality, as in typical beta-turns. In the hydrogen-bonding solvent DMSO, the in tramolecular hydrogen bond was still present, according to the tempera ture dependence of the chemical shift. The presence of the i, i + 3 hy drogen bond in the conjugates of mimic 1 was substantiated by the spec tral properties of conjugates of the isomeric mimic 3, which showed no evidence for the presence of an intramolecular hydrogen bond. The res ults from these studies suggest that the intramolecularly hydrogen-bon ded type via turn is an inherently more stable conformation for a pept ide than the non-hydrogen-bonded type VIb conformation, in the absence of other structural constraints.