Peptides constrained to type VI beta-turns .2. Antiparallel beta-ladder formation

The preparation and characterization of an extensive series of bis-amino acid conjugates of a novel beta-turn mimic are described. The conjugates were prepared by coupling amino acid residues to the amino and carboxyl groups of the mimic, which represented the central two residues of a peptide constrained to the type VI turn conformation. The resultant adducts had the capability to form either singly or doubly hydrogen-bonded conformations, which represented beta-turn or antiparallel beta-ladder structures, respectively. In the majority of the bis-amino acid conjugates of the cis-lactam 1 (or its enantiomer), only the interior hydrogen bond, characteristic of the singly hydrogen-bonded conformation, was present, according to NMR and IR spectra. When the lactam 1 or its enantiomer were coupled to L-Phe at its carboxyl group and N-AcGly at its amino group, the spectral properties indicated the presence of the doubly hydrogen-bonded form. The results are consistent with other corkers' studies that demonstrated that aryl residues following Pro stabilize antiparallel type VI turn structures and that the propensity of an amino acid to adopt a beta-conformation in proteins is highly dependent on context.