THE ROLE OF DEHYDRO-ALANINE IN THE DESIGN OF PEPTIDES

X-ray crystallography, NMR spectroscopy and theoretical studies on som e oligopeptides containing dehydro-alanine (Delta Ala) have indicated that Delta Ala adopts an extended conformation and also induces a defi nite conformation in the preceding saturated residue. In order to eval uate the conformational constraints imposed by Delta Ala on the neighb ouring saturated residues, we have undertaken a systematic, theoretica l study of the preferred conformations of tripeptide sequences of the type N-Ac-X-Delta Ala-NHCH3 and N-Ac-Delta Ala-X-NHCH3 (X = Gly, L-Ala , L-Val, L-Ile and L-Phe). The methodology and parameters used have be en standardized against sequences with known crystal structures. The s ignificant findings of this study are that Delta Ala always adopts an extended conformation and induces in both the preceding and the succee ding neighbouring saturated residues a conformation in which phi appro ximate to 140 degrees and psi approximate to - 40 degrees. These resul ts have a direct application in the design of peptide sequences for sp ecific biological activity.