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

The chemical synthesis and x‐ray crystal structure analysis of a model peptide incorporating a conformationally adaptable unsubstituted β‐Ala residue: Boc–β‐Ala–Acc 6 –OCH 3 (C 16 H 28 N 2 O 5 , 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), α = β = γ = 90.0°, Z = 4. An attractive feature of the crystal structure analysis of 1 is an accommodation of a significantly folded β‐Ala residue in a short linear peptide. The overall peptide conformation is typically folded into a β‐turn‐like motif. The stabilization of the peptide backbone conformation by nonconventional CH…O weak intramolecular hydrogen‐bonding interactions, involving the ester terminal carbon atom and the ethereal oxygen of the Boc group, has been evoked. The conformational constraint that seems most apparent is the ϕ, ψ value of the highly constrained hydrophobic Acc 6 ring that may play a key role in inducing or sustaining the observed pseudo type III or III′ β‐turn structure. The resulting 12‐membered hydrogen bonding ring motif in 1 is distinctly different from the one found in classical β‐turn structures, stabilized by a conventional strong CO…HN intramolecular hydrogen bond, comprised of α‐amino acids. The potential of the conformationally adaptable β‐Ala residue to occupy i + 1 position (left corner) of the folded β‐turn‐like structure and to design and construct novel secondary structural features have been emphasized. © 2000 John Wiley & Sons, Inc. Biopoly 53: 447–454, 2000