Chugai Seiyaku Kabushiki Kaisha

Mikimasa Tanada

Takashi Emura

Atsushi Matsuo

Koji Takano

Tatsuya Kato

Kaori Kimura

Atsushi Ohta

Tetsuo Kojima

Kenichi Nomura

Hitoshi Iikura

Yusuke Yamagishi

Ryuichi Takeyama

Naoaki Murao

Kazuhiko Nakano

Miki Kojima

Kousuke Asou

Takuya Torizawa

Ryusuke Takano

Nozomi Hisada

Takeo Iida

Shiori Kariyuki

Terushige Muraoka

Takuya Shiraishi

Toshiya Ito

Minoru Tamiya

Aya Chiyoda

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 inventors found cyclic peptide compounds that interact with Ras, and non-natural amino acids useful for the production of the cyclic peptide compounds. The inventors also found that the cyclic peptide compounds inhibit the binding between Ras and SOS. In addition, the inventors found specific non-natural amino acids contained in the cyclic peptide compounds and methods for production thereof.

Cyclic peptide compound having Kras inhibitory action

Methods of producing a peptide containing an N-substituted amino acid or N-substituted amino acid analog of the present invention include the steps of: preparing an Fmoc-protected amino acid, an Fmoc-protected amino acid analog, or an Fmoc-protected peptide; deprotecting a protecting group which have an Fmoc skeleton of the Fmoc-protected amino acid and such by using a base; and forming an amide bond by adding a new Fmoc-protected amino acid and such; and when the peptide is produced by a solid-phase method, the obtained peptide is cleaved off from the solid phase under conditions of weaker acidity than TFA. Furthermore, at least one side chain of the obtained peptide has a protecting group that is not deprotected under basic conditions and is deprotected under conditions of weaker acidity than TFA.

Method for synthesizing peptide containing N-substituted amino acid

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Shizuoka, Japan

Mikimasa Tanada