Functionalized Helical β‑Peptoids

• Published in: Journal of organic chemistry 2019-04, Vol.84 (7), p.3762-3779
• Main Authors: Wellhöfer, Isabelle, Frydenvang, Karla, Kotesova, Simona, Christiansen, Andreas M, Laursen, Jonas S, Olsen, Christian A
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.9b00218

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.