Theoretical and Experimental Studies on α/ε-Hybrid Peptides: Design of a 14/12-Helix from Peptides with Alternating (S)-C-Linked Carbo-E-amino Acid [(S)-ε-Caa_(X)] and L-Ala

摘要

An (S)-C-linked carbo-e-amino acid [(S)-ε-Caa_((x))] was prepared from the known (S)-δ-Caa. This monomer was utilized together with L-Ala to give novel α/ε-hybrid peptides in 1:1 alternation. Conformational analysis on penta- and hexapeptides by NMR (in CDCl_3), CD, and MD studies led to the identification of robust 14/12-mixed helices. This is in agreement with the data from a theoretical conformational analysis on the basis of ab initio MO theory providing a complete overview on all formally possible hydrogen-bonded helix patterns of α/ε-hybrid peptides with 1:1 backbone alterna_tion. The "new motif” of a mixed 14/12-helix was predicted as most stable in vacuum. Obviously, the formation of ordered secondary structures is also possible in peptide foldamers with amino acid constituents of considerable backbone lengths. Thus, a/c-hybrid peptides expand the domain of foldamers and allow the introduction of desired functionalities via the α-amino acid constituents.