Stabilization of a novel beta-turn-like motif by nonconventional intramolecular hydrogen-bonding interactions in a model peptide incorporating beta-alanine

The chemical synthesis and x-ray crystal structure analysis of a model pept ide incorporating a conformationally adaptable unsubstituted beta-Ala resid ue: Boc-beta-Ala-Acc(6)-OCH3 (C16H28N2O5, molecular weight = 328.41; 1) has been described. The peptide crystallized in the space group P2(1)2(1)2(1) a = 8.537 (3), b = 8.872 (10), c = 25.327 (8), alpha = beta = gamma = 90.0 degrees, Z = 4. An attractive feature of the crystal structure analysis of I is an accommodation of a significantly folded beta-Ala residue in a short linens peptide. The overall peptide conformation is typically folded into a beta-turn-like motif: The stabilization of the peptide backbone conformat ion by nonconventional C-H ... O weak intramolecular hydrogen-bonding inter actions, involving the ester terminal carbon atom and the ethereal oxygen o f the Boc group, has been evoked The conformational constraint that seems m ost apparent is the phi, psi, value of the the highly constrained hydrophob ic Acc(6) ring that may play a key role in inducing or sustaining the obser ved pseudo type III or III' beta-turn structure. The resulting 12-membered hydrogen bonding ring motif in I is distinctly different from the one found in classical beta-turn structures, stabilized by a conventional strong C=O ... H-N intramolecular hydrogen bond, comprised of alpha-amino acids. The potential of the conformationally adaptable beta-Ala residue to occupy i I position (left corner) of the folded beta-turn-like structure and to desi gn and construct novel secondary structural features have been emphasized. (C) 2000 John Wiley & Sons, Inc.