Functionalized Helical β‑Peptoids

Peptidomimetic foldamers adopting
well-defined three-dimensional
structures while being stable toward proteolysis are of interest in
biomedical research, chemical biology, and biomimetic materials science.
Despite their backbone flexibility, β-peptoids containing N-(S)-1-(1-naphthyl)­ethyl (Ns1npe) side chains can fold into unique triangular prism-shaped helices.
We report herein the successful introduction of amino groups onto
robustly folded β-peptoid helices by construction and incorporation
of novel chiral building blocks. This is the first example of an X-ray
crystal structure of a linear β-peptoid containing more than
one type of side chain. We thus present a unique foldamer design comprising
a robustly folded core with functionalized side chains protruding
perpendicular to the helical axis to provide a highly predictable
display of functional groups. This work paves the way for development
of β-peptoid foldamers with a desired function, such as catalytic
properties or as scaffolds enabling polyvalent display.