Helix Formation and Folding in <i>γ</i>‐Peptides and Their Vinylogues

Abstract

Abstract A complete overview of all possible periodic structures with characteristic H‐bonding patterns is provided for oligomers composed of γ ‐amino acids ( γ ‐peptides) and their vinylogues by a systematic conformational search on hexamer model compounds employing ab initio MO theory at various levels of approximation (HF/6‐31G*, DFT/B3LYP/6‐31G*, SCRF/HF/6‐31G*, PCM//HF/6‐31G*). A wide variety of structures with definite backbone conformations and H‐bonds formed in forward and backward directions along the sequence was found in this class of foldamers. All formally conceivable H‐bonded pseudocycles between 7‐ and 24‐membered rings are predicted in the periodic hexamer structures, which are mostly helices. The backbone elongation in comparison to α ‐ and β ‐peptides allows several possibilities to realize identical H‐bonding patterns. In good agreement with experimental data, helical structures with 14‐ and 9‐membered pseudocycles are most stable. It is shown that the introduction of an ( E )‐double bond into the backbone of the γ ‐amino acid constituents, which leads to vinylogous γ ‐amino acids, supports the folding into helices with larger H‐bonded pseudocycles in the resulting vinylogous γ ‐peptides. Due to the considerable potential for secondary‐structure formation, γ ‐peptides and their vinylogues might be useful tools in peptide and protein design and even in material sciences.