Helical peptide-foldamers having a chiral five-membered ring amino acid with two azido functional groups.

Abstract

A chiral five-membered ring α,α-disubstituted α-amino acid (R,R)-Ac5c(dN3) having two azido functional groups has been designed and synthesized. The cyclic amino acid (R,R)-Ac5c(dN3) could be efficiently converted into several cyclic amino acids with various two 1,2,3-triazole functional groups. (R,R)-Ac5c(dN3) homochiral peptides (up to hexapeptide) and (R,R)-Ac5c(dN3)-containing l-Leu-based peptides were prepared, and their conversion of azido functional groups into triazole groups was completed. The preferred conformation of oligomers, before and after the "click reaction", together with the azido gauche effect of amino acid residues were studied using FT-IR absorption, CD, (1)H NMR, and X-ray crystallographic analysis. The cyclic amino acid (R,R)-Ac5c(dN3) could be used as a helical conformation controlling residue and also has a versatile functionalizing site in its oligopeptides.