Conformational study of peptides containing dehydrophenylalanine Helical structures without hydrogen bond

Abstract

The conformational behaviour of ∆^zPhe has been investigated in the model dipeptide Ac-∆^z Phe-NHMe and in the model tripeptides Ac-X-∆^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 <img src='/image/spc_char/phi.gif' border=0>₁=-30°, <span style="font-size:14.0pt;mso-bidi-font-size:12.0pt" lang="EN-IN">ψ₁= 120° and <img src='/image/spc_char/phi.gif' border=0>₂₌<span style="font-size:14.0pt;mso-bidi-font-size:12.0pt" lang="EN-IN">ψ₂ =30°. 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 3₁₀ helical structure. In the peptides Ac- Aib-∆^z Phe-NHMe and Ac-(Aib-∆^z Phe)₃-NHMe, the helical conformers with <img src='/image/spc_char/phi.gif' border=0>=±30°, <span style="font-size:14.0pt;mso-bidi-font-size: 12.0pt" lang="EN-IN">ψ= ±60° for Aib residue and <img src='/image/spc_char/phi.gif' border=0>= <span style="font-size:14.0pt;mso-bidi-font-size:12.0pt" lang="EN-IN">ψ= ±30° for ∆^z Phe are predicted to be most stable. The computational studies for the positional preferences of ∆^z Phe residue in the peptide containing one ∆^z Phe and nine Ala residues reveal the formation of a 3₁₀ helical structure in all the cases with terminal preferences for ∆^zPhe. The conformational behaviour of Ac-(∆^z Phe)_n-NHM_e with n≤4 is predicted to bc very labile. With n> 4, degenerate conformational states with <span style="font-size:16.0pt; font-family:Symbol;mso-ascii-font-family:" arial="" unicode="" ms";mso-hansi-font-family:="" "arial="" ms";mso-char-type:symbol;mso-symbol-font-family:symbol"="" lang="EN-IN">j, <span style="font-size:14.0pt;mso-bidi-font-size: 12.0pt" lang="EN-IN">ψ values of 0° ± 90° adopt helical structures which are stabilized by carbonyl-carbonyl interactions and the N-H-<span style="font-size:14.0pt;mso-bidi-font-size:12.0pt" lang="EN-IN">π interactions between the amino group of every ∆^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 ∆^z Phe residues is ambiguous in solution. The helical structures stabilized by hydrogen bond formation are found to be at least 3kCalmol^-1 less stable. Conformational studies have also been carried out for the peptide Ac-(∆^E Phe)₆,-NHMe and the peptide Ac-∆Ala- (∆^z Phe)₆-NHMe containing ∆Ala residue at the N-terminal. The N-H -<span style="font-size:14.0pt;mso-bidi-font-size:12.0pt" lang="EN-IN">π interactions are absent in peptide Ac-(∆^E Phe)₆-NHMe.

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