Strengthening Peptoid Helicity through Sequence Site-Specific Positioning of Amide -Inducing Bu Monomers.

The synthesis of biomimetic helical secondary structures is sought after for the construction of innovative nanomaterials and applications in medicinal chemistry such as the development of protein-protein interaction modulators. Peptoids, a sequence-defined family of oligomers, enable a peptidomimetic strategy, especially considering the easily accessible monomer diversity and peptoid helical folding propensity. However, - isomerization of the backbone tertiary amides may impair the peptoid's adoption of stable secondary structures, notably the all- polyproline I-like helical conformation. Here, we show that -inducing Bu achiral monomers strategically positioned within chiral sequences may reinforce the degree of peptoid helicity, although with a reduced content of chiral side chains. The design principles presented here will undoubtedly help achieve more conformationally stable helical peptoids with desired functions.