Glytech, Inc.

Otsuka Chemical Co., Ltd.

Otsuka Chemical Holdings Co., Ltd.

Yuri Nambu

Yasuhiro Kajihara

Kazuhiro Fukae

Hiroaki Asai

Izumi Sakamoto

Takashi Tsuji

Katsunari Tezuka

Kazuyuki Ishii

Naohiro Hayashi

Naoki Yamamoto

The present invention provides a method for producing a peptide, characterized in that it comprises converting an &#x2014;SH group of a peptide comprising an amino acid residue having the &#x2014;SH group to an &#x2014;OH group, wherein said method comprises the following steps (a) to (c): (a) allowing an &#x2014;SH group in a peptide to react with a methylating agent to convert the &#x2014;SH group to an -SMe group; (b) allowing the -SMe group obtained in the step (a) to react with a cyanizing agent to produce a reaction intermediate; and (c) converting the reaction intermediate obtained in the step (b) to a peptide comprising an amino acid residue having an &#x2014;OH group under more basic conditions than the conditions in the step (b).

Method for producing peptide

Oligosaccharide chain added GLP-1 peptides are more stable in blood and more active in controlling blood-sugar levels than GLP-1 peptides without added oligosaccharides. Oligosaccharide chain added GLP-1 peptides having GLP-1 activity include at least one or at least two amino acids each substituted with an oligosaccharide chain added amino acid in GLP-1; a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or a GLP-1 analog. Oligosaccharide chain added GLP-1 peptides with at least one amino acid substituted with an oligosaccharide chain added amino acid include an oligosaccharide chain with oligo hyaluronic acid. Oligosaccharide chain added amino acids include oligosaccharide chains attached to amino acids via linkers.

Glycosylated GLP-1 peptide

The present invention relates to an oligosaccharide chain added GLP-1 peptide that has higher stability in blood than that of GLP-1 and, preferably, exhibits higher activity of controlling blood-sugar levels than that of GLP-1. The present invention relates to an oligosaccharide chain added GLP-1 peptide having GLP-1 activity, wherein at least one amino acid is substituted with an oligosaccharide chain added amino acid, in: (a) GLP-1; (b) a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or (c) a GLP-1 analog.

Sugar chain added GLP-1 peptide

The present invention provides a process for producing a peptide thioester compound. The process involves: (A) forming a peptide by a solid-phase synthesis method using a resin modified with a linker represented by the formula (1) as a solid phase: wherein Rrepresents Calkyl group, Rrepresents hydrogen atom or Calkoxy group, and n represents an integer of 1 to 4; (B) cleaving a bond between the solid phase and the peptide with at least one acid selected from dilute hydrochloric acid, dilute sulfuric acid, formic acid, and acetic acid to produce a peptide having a carboxyl group at the C-terminus; and (C) reacting a thiol compound with the peptide at &#x2212;100 to 0&#xb0; C. in the presence of a condensing agent in a solvent.

Method for production of peptide thioester compound

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Tokushima, Japan

Yuri Nambu