Glytech, Inc.

Otsuka Chemical Co., Ltd.

Other

Otsuka Chemical Holdings Co., Ltd.

Kajihara, Yasuhiro

Kazuhiro Fukae

Yasuhiro Kajihara

Katsunari Tezuka

Masatoshi Maeda

Izumi Sakamoto

Hiroaki Asai

Keisuke Tazuru

Yuri Nambu

Takashi Tsuji

Hirofumi Ochiai

Taiji Shimoda

Kenta Yoshida

Kazuyuki Ishii

Kazuaki Kakehi

Hiroaki Maeda

Hisashi Narimatsu

Yasunori Chiba

Yoshie Takahashi

Naohiro Hayashi

Naoki Yamamoto

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

[Problem] To provide a glycosylated polypeptide having an affinity to somatostatin receptors, and, compared to somatostatins, having improved in-blood stability. [Solution] The glycosylated polypeptide is characterized by at least one amino acid in a somatostatin or an analog thereof being replaced with a glycosylated amino acid.

Glycosylated polypeptide and drug composition containing said polypeptide

[Problem] To provide a glycosylated polypeptide having affinity to somatostatin receptors and, compared to somatostatins, having improved in-blood stability. [Solution] The glycosylated polypeptide is characterized by at least two amino acids in a somatostatin or an analog thereof being replaced by glycosylated amino acids.

[Problem] To provide a glycosylated polypeptide having affinity to somatostatin receptors and, compared to somatostatins, having improved in-blood stability. [Solution] The glycosylated polypeptide is characterized by at least two amino acids in a somatostatin or an analogue thereof being replaced by glycosylated amino acids.

[Problem to be Solved] The importance of sugar chains having &#x3b1;2,3- or &#x3b1;2,6-linked sialic acid at their non-reducing ends is known. Industrial production has been demanded for these sugar chain compounds. Particularly, the production of glycoprotein drugs or the like inevitably requires producing in quantity sugar chains having homogeneous structures by controlling the linking pattern (&#x3b1;2,6-linkage or &#x3b1;2,3-linkage) of sialic acid. Particularly, a triantennary or tetraantennary N-type complex sugar chain having sialic acid at each of all non-reducing ends is generally considered difficult to chemically synthesize. There has been no report disclosing that such a sugar chain was chemically synthesized. Furthermore, these sugar chains are also difficult to efficiently prepare enzymatically. [Solution] The present inventors have newly found the activity of sialyltransferase of degrading sialic acid on a reaction product in the presence of CMP and also found that formed CMP can be degraded enzymatically to thereby efficiently produce a sialic acid-containing sugar chain. The present inventors have further found that even a tetraantennary N-type sugar chain having four &#x3b1;2,6-linked sialic acid molecules, which has previously been difficult to synthesize, can be prepared at high yields by one-pot synthesis comprising the elongation reaction of a biantennary sugar chain used as a starting material without performing purification after each enzymatic reaction.

Method for producing sialic-acid-containing sugar chain

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

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

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

A process for preparing asparagine-linked oligosaccharide derivatives including the steps of: (a) treating a delipidated egg yolk with a protease to obtain a mixture of peptide-linked oligosaccharides, (b) treating the mixture of peptide-linked oligosaccharides with a peptidase to obtain a mixture of asparagine-linked oligosaccharides, (c) introducing a lipophilic protective group into the asparagine-linked oligosaccharides in the mixture to obtain a mixture of asparagine-linked oligosaccharide derivatives, and (d) subjecting the mixture of asparagine-linked oligosaccharide derivatives to chromatography to separate the mixture into individual asparagine-linked oligosaccharide derivatives.

Process for producing sugar chain asparagine derivative

An aminated complex-type oligosaccharide derivative of the formula (1) wherein Ris H&#x2014;(CO)&#x2014;CHX, &#x2014;NH&#x2014;(CO)&#x2014;(CH)&#x2014;CHX, isothiocyanate group, &#x2014;NH&#x2014;(CO)&#x2014;(CH)&#x2014;COH or &#x2014;NH&#x2014;(CO)&#x2014;(CH)&#x2014;CHO, X being a halogen atom, a being 0 or 1, b being an integer of 1 to 4, Rand Rare a hydrogen atom or a group of the formulae (2) to (5) and may be the same or different, except for the case where both Rand Rare hydrogen or the formula (5), and the case where one of Rand Ris a hydrogen atom, with the formula (5) serving as the other thereof.

Aminated complex-type sugar chain derivatives and process for the production thereof

An asparagine-linked disialoundecaoligosaccharide-fatty acid amide, a drug containing the same, and a drug containing an asparagine-linked disialoundecaoligosaccharide.

Growing community of inventors

Tokushima, Japan

Kazuhiro Fukae