Oligo(4-aminopiperidine-4-carboxylic acid): An unusual basic oligopeptide with an acid-induced helical conformation

In sharp contrast with helical polypeptides carrying basic side chains, Api₈, a basic oligopeptide containing the non-natural achiral amino acid 4-aminopiperidine-4-carboxylic acid (Api), adopts a helical conformation only in acidic media. Alkaline titration of a protonated Api₈ oligomer appended with a leucine derivative at its N-terminus showed that disruption of its helical conformation occurs in a pH range of 7-10. NMR studies indicated that the piperidine groups in Api₈, when nonprotonated, possibly interact with the proximal amide protons in the peptide backbone and hamper the formation of the H-bonding network responsible for the helical conformation. The helical structure is induced not only by protonation but also by acylation of the piperidine groups.