Conformational Study Of Peptides Containing Dehydrophenylalanine: Helical Structures Without Hydrogen Bond

The conformational behaviour of Delta (z)Phe has been investigated in the model dipeptide Ac-Delta (z)Phe-NHMe and in the model tripeptides Ac-X-Delta (z)Phe-NHMe with X=Gly,Ala,Val,Leu,Abu,Aib and Phe and is found to be quite different. In the model tripeptides with X=Ala,Val,Leu,Abu,Phe the most stable structure 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 formation between C=O of acetyl group and the NH of the amide group, resulting in the formation of a 10-membered ring but not a 3(10) helical structure. In the peptides Ac-Aib-Delta (z)Phe-NHMe and Ac-(Aib-Delta (z)Phe)(3)-NHMe, the helical conformers with phi= +/-30 degrees, psi= +/-60 degrees for Aib residue and phi=psi= +/-30 degrees for Delta (z)Phe are predicted to be most stable. The computational studies for the positional preferences of Delta (z)Phe residue in the peptide containing one Delta (z)Phe and nine Ala residues reveal the formation of a 3(10) helical structure in all the cases with terminal preferences for Delta (z)Phe. The conformational behaviour of Ac-(Delta (z)Phe)(n)-NHMe with n less than or equal to4 is predicted to be very labile. With n > 4, degenerate conformational states with phi,psi values of 0 degrees +/- 90 degrees adopt helical structures which are stabilized by carbonyl-carbonyl interactions and the N-H-pi interactions between the amino group of every Delta (z)Phe residue with one C-C edge of its own phenyl ring. The results are in agreement with the experimental finding that screw sense of helix for peptides containing Delta (z)Phe residues is ambiguous in solution. The helical structures stabilized by hydrogen bond formation are found to be atleast 3kCalmol(-1) less stable. Conformational studies have also been carried out for the peptide Ac-(Delta (epsilon)Phe)(6)-NHMe and the peptide Ac-Delta Ala-(Delta (z)Phe)(6)-NHMe containing Delta Ala residue at the N-terminal, The N-H-pi interactions are absent in peptide Ac-(Delta (E)phe)(6)-NHMe.