Glytech, Inc.

Otsuka Chemical Co., Ltd.

Other

Japan Tobacco Inc.

Otsuka Chemical Holdings Co., Ltd.

Yasuhiro Kajihara

Kajihara, Yasuhiro

Ken Sasaki

Kazuhiro Fukae

Izumi Sakamoto

Katsunari Tezuka

Hiroaki Asai

Yuri Nambu

Takashi Tsuji

Kazuyuki Ishii

Takefumi Murase

Ryo Okamoto

Kazuaki Kakehi

Masatoshi Maeda

Hisashi Kodama

Hiroaki Maeda

Takashi Ebata

Keisuke Tazuru

Masaki Ohuchi

Naohiro Hayashi

Mika Nishihara

Yasuhito Morishita

Naoki Yamamoto

Akihiro Manbo

Hironobu Hashimoto

Yoko Amazaki

Rie Nishikawa

Kota Nomura

Masayuki Izumi

Takuya Haraguchi

Yuta Maki

Masumi Murakami

Motoharu Kimura

Kazuhiro c/o Otsuka Chemical Co Ltd Fukae

Kazuhiro Otsuka Chemical Co Ltd Fukae

Hiroaki Sanyo Chemical Industries Ltd Maeda

An object of the present invention is to provide a novel method having high efficiency and versatility for a peptide thioester and peptide. The present invention provides a method for producing a peptide thioester, comprising the steps of: (1) providing a peptide thioester having a CGC triplet at the C-terminal; (2) causing a transfer between an SH group of the C-terminal cysteine and a carbonyl group of the glycine in the CGC triplet to obtain an R-X-CG-thioester; and (3) causing, in the R-X-CG-thioester, a transfer between the SH group of the cysteine and a carbonyl group of X, and a transfer between an amino group of the cysteine and a thiol group of the glycine to obtain a peptide thioester, and a method for producing a peptide using the peptide thioester produced by this method.

Methods for producing peptide thioester and peptide

The object of the present invention is to provide a method for manufacturing an amino acid polymer more simply and efficiently compared to conventional methods for manufacturing amino acid polymers. The present invention provides a method for manufacturing an amino acid polymer with thioacid amino acids. Specifically, the manufacturing method of the present invention comprises (A) a step of preparing first and second thioacid amino acids, (B) a step of subjecting said first and second thioacid amino acids to an oxidation reaction to obtain an amino acid polymer linked by peptide bonds. The manufacturing method of the present invention is characterized in that it partially uses thioacid amino acids that do not possess a protecting group.

Production method for amino-acid polymer

An object of the invention is to provide a method of uniformly and efficiently producing a saccharide having a sulfate group and/or a phosphate group in the molecule, or a compound containing the saccharide. [Solution] The present invention provides a method of producing a saccharide having a sulfate group and/or a phosphate group. The method comprises (a) a step of preparing a 'first saccharide having a non-protected sulfate group and/or a non-protected phosphate group' and a 'second saccharide having a non-protected sulfate group and/or a non-protected phosphate group' and (b) a step of condensing the first saccharide and the second saccharide prepared in the step (a) with each other.

Method for producing sugar having sulfate group and/or phosphate group

The object of the present invention is to provide a glycosylated polypeptide having uniform sugar chain structure which has interferon &#x3b2; activity. It was found that a glycosylated polypeptide having uniform sugar chain structure as well as having interferon &#x3b2; activity can be prepared by a method comprising a step of synthesizing a glycosylated peptide fragment and at least two peptide fragments and a step of linking the glycosylated peptide fragment and the at least two peptide fragments.

Glycosylated polypeptide and pharmaceutical composition containing same

The object of the present invention is to provide a polypeptide having interferon &#x3b2; activity glycosylated with highly uniform sialylated sugar chains. The present invention is a glycosylated polypeptide, wherein the polypeptide is any polypeptide selected from the group consisting of the following (1) to (4); (1) a polypeptide consisting of the amino acid sequence represented by SEQ ID NO. 1, (2) a polypeptide having one or a few amino acids deleted, substituted, or added in the polypeptide consisting of the amino acid sequence represented by SEQ ID NO. 1, (3) a polypeptide that is an analog of interferon &#x3b2;, and (4) a polypeptide having 80% or more homology to the polypeptide consisting of the amino acid sequence represented by SEQ ID NO. 1, in which amino acids at 4 to 6 locations are substituted with glycosylated amino acids, and wherein all of the non-reducing terminals of said sugar chain are sialylated.

Polypeptide having sialylated sugar chains attached thereto

The object of the present invention is to provide a method of efficiently manufacturing an optically active D- and/or L-form amino acid possessing a thiol group in the side chain by a simple method. The present invention provides a method of manufacturing an amino acid derivative possessing a thiol group in the side chain, characterized in manufacturing an intermediate composition comprising D- and L-forms of an amino acid derivative possessing a thiol group at the &#x3b2;-position, reacting a hydrolase selective for D- or L-amino acids, and separating the hydrolyzed D- or L-amino acid derivative, as well as an intermediate thereof.

Method for producing D-form or L-form amino acid derivative having thiol group

A process for chemically converting a peptide chain into a peptide thioester includes, when a &#x2014;C(&#x2550;X)&#x2014;Rgroup is introduced to the thiol group of the cysteine residue and then the resulting peptide is reacted with a compound having a leaving group represented by the formula: &#x2014;NH&#x2014;C(&#x2550;Y)NHRin an organic solvent, the &#x2014;NH&#x2014;C(&#x2550;Y)NHRgroup binds via addition reaction to the carboxyl group of the N-terminal-side peptide bond of the cysteine residue, whereby the peptide bond is cleaved and the C-terminal-side peptide fragment is cut off. Further, when the resulting peptide chain having the &#x2014;NH&#x2014;C(&#x2550;Y)NHRgroup is reacted with a thiol in a buffer solution, a thiol exchange reaction occurs, namely, the thiol group of the thiol binds to the carbonyl carbon to which the &#x2014;NH&#x2014;C(&#x2550;Y)NHRgroup has bound, whereby the &#x2014;NH&#x2014;C(&#x2550;Y)NHRgroup is eliminated.

Process for production of peptide thioester

[Technical Problem] To provide a method for manufacturing that enables to obtain a targeted glycopeptide harboring a sialyl sugar chain in high yield without decomposing sialic acid at a non-reducing terminal of sugar chain when the glycopeptide is synthesized by a Boc solid phase synthesis method. [Solution to Problem] The present invention is characterized in that the Boc-sialylglycosylated amino acid derivative used in Boc solid phase synthesis method is one where the carboxyl group of the sialic acid at the sugar chain non-reducing terminal is protected with a phenacyl group.

Method for producing glycopeptide having sialyl sugar chain, sialyl sugar chain-added amino acid derivative to be used in same, and glycopeptide

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

Glycopeptide having at least one asparagine-linked oligosaccharide at a desired position of the peptide chain obtained by:

Process for preparing glycopeptides having asparagine-linked oligosaccharides, and the glycopeptides

An asparagine-linked &#x3b1;2,3-oligosaccharide having undeca- to hepta-saccharides, an asparagine-linked &#x3b1;2,6-oligosaccharide having undeca- to hepta-saccharides and containing fluorine and an asparagine-linked oligosaccharide derivative containing at least one fucose in N-acetylglucosamine on the nonreducing terminal side of an asparagine-linked oligosaccharide wherein the asparagine has amino group protected with a lipophilic protective group, and a process for producing these compounds.

Sugar chain asparagine derivatives, sugar chain asparagine, sugar chain and processes for producing these

Growing community of inventors

Yokohama, Japan

Yasuhiro Kajihara