Construction of ordered self assembled architectures from peptide foldamers composed of non natural amino acids

Abstract

Inspired by the functions of proteins and metalloproteins, extensive efforts have been made over the years to mimic their structures and functions using non-natural amino acid building blocks. The folded structures derived from the oligomers of beta, gamma, and delta amino acids and their mixed sequences along with alpha-amino acids offer a wide range of structural diversity with potential applications in biology and materials. In our previous studies, we have shown the remarkable beta-double helical structures from the homo-oligomers of 4,4-dimethyl substituted (E)-vinylogous amino acids and stable helical structures from short sequences of alpha, gamma-hybrid peptides. However, understanding the requirement of amino acid residues and peptide sequences to form a double helical structure was an illusion. In the present study, we have revealed that the beta-double helical structures not confined to the oligomers 4,4-dimethyl substituted (E)-vinylogous amino acids, even the mixed sequences composed of 3,3-dimethyl substituted gamma-amino acid (Adb) along with 4,4-dimethyl substituted (E)- vinylogous amino acids and also form artificial beta double-helical structures. In sharp contrast, replacing 3,3-dimethyl gamma-amino acids with 4,4-dimethyl gamma-amino acids also leads to double helical structures. The structural analysis of the double helix shows achiral in nature. Furthermore, we have examined the transformation of the achiral nature of the beta-double helices into chiral double helices by attaching chiral amines at the C-terminal of the peptides. Both single crystal structure and solution state analysis reveal that even after attaching a chiral amine, the peptide maintained its double helical nature, and chirality is induced throughout the peptide sequences. In contrast to the double helical structures, the alpha-gamma-alpha-hybrid tripeptides composed of saturated gamma-amino acids gave stable helical structures in single crystals and solution state. We have examined these stable helical structures