Sulfono-γ-AApeptides as a New Class of Nonnatural Helical Foldamer

Foldamers offer an attractive opportunity for the design of novel molecules that mimic the structures and functions of proteins and enzymes including biocatalysis and biomolecular recognition. Herein we report a new class of nonnatural helical sulfono‐γ‐AApeptide foldamers of varying lengths. The crystal structure of the sulfono‐γ‐AApeptide monomer S6 illustrates the intrinsic folding propensity of sulfono‐γ‐AApeptides, which likely originates from the bulkiness of tertiary sulfonamide moiety. The two‐dimensional solution NMR spectroscopy data for the longest sequence S1 demonstrates a 10/16 right‐handed helical structure. Optical analysis using circular dichroism further supports well‐ defined helical conformation of sulfono‐γ‐AApeptides in solution containing as few as five building blocks. Future development of sulfono‐γ‐AApeptides may lead to new foldamers with discrete functions, enabling expanded application in chemical biology and biomedical sciences. New helical foldamer: A new class of nonnatural helical sulfono‐γ‐AApeptide foldamer of varying lengths has been developed. The two‐dimensional solution NMR spectroscopy data for the longest sequence demonstrates a 10/16 right‐handed helical structure. In each sulfono‐γ‐AApeptide, the residues from the N‐terminus are numbered 1, 2, etc. In each sulfono‐γ‐AApeptide residue, a denotes the chiral side chain derived from the cognate α‐amino acid, and b represents the sulfonyl side group coming from sulfonyl chlorides (see scheme).