Chugai Seiyaku Kabushiki Kaisha

The University of Tokyo

Yusuke Yamagishi

Atsushi Ohta

Atsushi Matsuo

Tatsuya Kato

Kaori Kimura

Takashi Emura

Tetsuo Kojima

Hitoshi Iikura

Koji Takano

Mikimasa Tanada

Naoaki Murao

Ryuichi Takeyama

Kousuke Asou

Takuya Torizawa

Ryusuke Takano

Shiori Kariyuki

Nozomi Hisada

Takeo Iida

Miki Kojima

Kazuhiko Nakano

Hiroaki Suga

Takuya Shiraishi

Hiroshi Murakami

Yuki Goto

Hiroshi Ashigai

Yusuke Sako

An object of the present invention is to provide methods of discovering drugs effective for tough targets, which have conventionally been discovered only with difficulty. The present invention relates to novel methods for cyclizing peptide compounds, and novel peptide compounds and libraries comprising the same, to achieve the above object.

Peptide-compound cyclization method

The present invention provides modified aminoacyl-tRNA synthetases (ARSs) having increased reactivity with N-methyl amino acids compared to natural aminoacyl-tRNA synthetases. The modified aminoacyl-tRNA synthetases according to the present invention can aminoacylate tRNAs with their corresponding N-methyl-substituted amino acids such as N-methyl-phenylalanine, N-methyl-valine, N-methyl-serine, N-methyl-threonine, N-methyl-tryptophan and N-methyl-leucine more efficiently than natural aminoacyl-tRNA synthetases. The present invention enables a more efficient production of polypeptides containing N-methyl amino acids.

Modified aminoacyl-tRNA synthetase and use thereof

The present invention provides modified aminoacyl-tRNA synthetases (ARSs) having increased reactivity with N-methyl amino acids compared to natural aminoacyl-tRNA synthetases. The modified aminoacyl-tRNA synthetases according to the present invention can aminoacylate tRNAs with their corresponding N-methyl-substituted amino acids such as N-methyl-phenylalanine, N-methyl-valine, N-methyl-serine, N-methyl-threonine, N-methyl-tryptophan, and N-methyl-leucine more efficiently than natural aminoacyl-tRNA synthetases. The present invention enables a more efficient production of polypeptides containing N-methyl amino acids.

A method for screening a non-standard peptide compound in the peptide library that binds to the target substance, comprising the steps: (i) preparing a non-standard peptide library wherein a special (non-standard) amino acid is randomly incorporated into the peptide sequence by a cell-free (in vitro) translation system comprising a tRNA acylated by a special (non-standard) amino acid; (ii) bringing the obtained peptide library in contact with a target substance; and (iii) selecting a non-standard peptide that binds to the target substance as an active peptide.

Method for constructing libraries of non-standard peptide compounds comprising N-methyl amino acids and other special (non-standard) amino acids and method for searching and identifying active species

The objective is to provide a novel process for synthesizing a cyclic peptide compound. It is also an objective to provide a novel cyclic peptide compound. The novel process for synthesizing a cyclic peptide compound comprises the steps of: (1) translationally synthesizing a non-cyclic peptide compound having in a molecule a functional group 1 and a functional group 2, which are a pair of functional groups capable of reacting to form a bond, and (2) cyclizing the non-cyclic peptide compound by the reaction of the functional groups 1 and 2 to form a bond. The novel cyclic peptide compound can be synthesized by the process.

Process for synthesizing cyclic peptide compound

Growing community of inventors

Kanagawa, Japan

Yusuke Yamagishi