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A Peptoid with Extended Shape in Water

preprint
submitted on 06.01.2019, 12:29 and posted on 08.01.2019, 14:57 by Jumpei Morimoto, Yasuhiro Fukuda, Takumu Watanabe, Daisuke Kuroda, Kouhei Tsumoto, Shinsuke Sando

“Peptoids” was proposed, over decades ago, as a term describing analogs of peptides that exhibit better physicochemical and pharmacokinetic properties than peptides. Oligo-(N-substituted glycines) (oligo-NSG) was previously proposed as a peptoid due to its high proteolytic resistance and membrane permeability. However, oligo-NSG is conformationally flexible and is difficult to achieve a defined shape in water. This conformational flexibility is severely limiting biological application of oligo-NSG. Here, we propose oligo-(N-substituted alanines) (oligo-NSA) as a new peptoid that forms a defined shape in water. A 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. The new class of peptoid achieves the constrained conformation without any assistance of N-substituents and serves as an ideal scaffold for displaying functional groups in well-defined three-dimensional space, which leads to effective biomolecular recognition.

Funding

JSPS (JP17K13265)

CREST (JPMJCR13L4), Japan Science and Technology Agency

JSPS (JP17K18113)

Japan Agency for Medical Research and development, AMED (JP18fm0208022h)

JSPS (JP16H02420)

JSPS (JM17H06109)

Japan Agency for Medical Research and development, AMED (JP18arn0101094j)

History

Email Address of Submitting Author

ssando@chembio.t.u-tokyo.ac.jp

Institution

The University of Tokyo

Country

Japan

ORCID For Submitting Author

0000-0003-0275-7237

Declaration of Conflict of Interest

The authors declare no conflict of interests.

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in Journal of the American Chemical Society

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