ja9b04371_si_002.cif (54.38 kB)
A Peptoid with Extended Shape in Water
dataset
posted on 2019-08-23, 19:14 authored by Jumpei Morimoto, Yasuhiro Fukuda, Daisuke Kuroda, Takumu Watanabe, Fumihiko Yoshida, Mizue Asada, Toshikazu Nakamura, Akinobu Senoo, Satoru Nagatoishi, Kouhei Tsumoto, Shinsuke SandoThe
term “peptoids” was introduced decades ago to
describe peptide analogues that exhibit better physicochemical and
pharmacokinetic properties than peptides. Oligo(N-substituted glycine) (oligo-NSG) was previously proposed as a peptoid
due to its high proteolytic resistance and membrane permeability.
However, oligo-NSG is conformationally flexible, and ensuring a defined
shape in water is difficult. This conformational flexibility severely
limits the biological application of oligo-NSG. Here, we propose oligo(N-substituted alanine) (oligo-NSA) as a peptoid that forms
a defined shape in water. The synthetic method established in this
study enabled the first isolation and conformational study of optically
pure oligo-NSA. Computational simulations, crystallographic studies,
and spectroscopic analysis demonstrated the well-defined extended
shape of oligo-NSA realized by backbone steric effects. This new class
of peptoid achieves the constrained conformation without any assistance
of N-substituents and serves as a scaffold for displaying
functional groups in well-defined three-dimensional space in water,
which leads to effective biomolecular recognition.