Conformational structure of peptides containing dehydroalanine: Formation of beta-bend ribbon structure

alpha,beta-Unsaturated amino acids (dehydroamino acids) have been found in naturally occurring antibiotics of microbial origin and in some proteins. D ue to the presence of the C-alpha=C-beta double bond, the dehydroamino acid s influence the main-chain and the side-chain conformations. The lowest-ene rgy conformational state of the model tripeptides, Ac-X-Delta Ala-NHMe, (X = Ala, Val, Leu, Abu, or Phe) corresponds to phi(1) = -30 degrees, psi(1) = 120 degrees and phi(2) = psi(2) = 30 degrees. This structure is stabilized by the hydrogen bond between C=O of the acetyl group and the NH of the ami de group, resulting in the formation of a 10-membered ring. in the model he ptapeptide containing Delta Ala at alternate position with Ala, Abu, and Le u, the lowest-energy conformation corresponds to phi = -30 degrees and psi = 120 degrees for all the Ala, Abu, and Leu residues and phi = psi = 30 deg rees for all Delta Ala residues. A graphical view of the molecule in this c onformation reveals the formation of three hydrogen bonds involving the C=O moiety of the ith residue and the NH moiety of the i + 3th residue, result ing in a 10-membered ring formation. Ln this structure, only alternate pept ide bonds are involved in the intramolecular hydrogen-bond formation unlike the helices and it has been named the P-bend ribbon structure. The helical structures were predicted to be the most stable structures in the heptapep tide Ac-(Aib-Delta Ala)(3)-NHMe with phi = +/-30 degrees, psi = +/-60 degre es for Aib residues and phi = psi = +/-30 degrees for Delta Ala residues. T he computational results reveal that the Delta Ala residue does not induce an inverse gamma-turn in the preceding residue. It is the competitive inter action of small solvent molecules with the hydrogen-bonding sites of the pe ptide which gives rise to the formation of an inverse gamma-turn (phi(1) = - 54 degrees, psi(1) = 82 degrees; phi(2) = 44 degrees, psi(2) = 3 degrees) in the preceding residue to Delta Ala. The computational studies for the p ositional preference of Delta Ala in the peptide containing one Delta Ala a nd nine Ala residues reveals the formation of a 3(10) helical structure in all the cases with the terminal preferences for Delta Ala, consistent with the position of Delta Ala in the natural antibiotics. The extended structur es is found to be the most stable for poly-Delta Ala. (C) 1999 John Wiley & Sons, Inc.