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A Peptoid with Extended Shape in Water

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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 Sando
The 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.

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