The role of dehydro-Alanine in the design of peptides

X-ray crystallography, NMR spectroscopy and theoretical studies on some oligopeptides containing dehydro-alanine (ΔAla) have indicated that ΔAla adopts an extended conformation and also induces a definite conformation in the preceding saturated residue. In order to evaluate the conformational constraints imposed by ΔAla on the neighbouring saturated residues, we have undertaken a systematic, theoretical study of the preferred conformations of tripeptide sequences of the type N-Ac-X-ΔAla-NHCH3 and N-Ac-ΔAla-X-NHCH3 (X = Gly, L-Ala, L-Val, L-Ile and L-Phe). The methodology and parameters used have been standardized against sequences with known crystal structures. The significant findings of this study are that ΔAla always adopts an extended conformation and induces in both the preceding and the succeeding neighbouring saturated residues a conformation in which θ ≈ 140° and ψ ≈ −40°. These results have a direct application in the design of peptide sequences for specific biological activity.