Strategic C to N Replacement in β-Peptides: Atomic Level Control of Helical Folding.

Single residue control of the helical topology of β-peptides is a contemporary challenge in foldamer science. We present the conformational preferences of oligomers of trans-2-aminocyclobutanecarboxylic acid ( tACBC), in which a central residue has been replaced by a single N-aminoazetidine-2-carboxylic acid (AAzC) moiety. The latter has such a strong demand for local 8-helical conformers that the usual 12-helix secondary structure of a tACBC octamer is switched to a fully 8-helical conformation as a result of the single residue substitution.