公开(公告)号：US12103947B2

公开(公告)日：2024-10-01

申请号：US17298125

申请日：2019-03-04

Applicant: GLYTECH, INC.

Inventor： Yasuhiro Kajihara ,  Ryo Okamoto ,  Yuta Maki ,  Yoko Amazaki ,  Kota Nomura ,  Rie Nishikawa ,  Takefumi Murase

IPC: C07K1/113

CPC classification number: C07K1/1133

Abstract: 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.

公开(公告)号：US10913763B2

公开(公告)日：2021-02-09

申请号：US16078861

申请日：2017-03-07

Applicant: GLYTECH, INC.

Inventor： Yasuhiro Kajihara ,  Akihiro Manbo ,  Takefumi Murase

IPC: C08B37/00 ,  C07H11/00 ,  C07H11/04 ,  C07H1/00 ,  C07H15/12 ,  C07H15/203 ,  C07H19/01

Abstract: 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.

公开(公告)号：US10683341B2

公开(公告)日：2020-06-16

申请号：US15740511

申请日：2016-06-30

Applicant: Glytech, Inc. ,  RIKEN

Inventor： Katsunori Tanaka ,  Yasuyoshi Watanabe ,  Akihiro Ogura ,  Takahiro Yamamoto

IPC: C07K14/765 ,  A61K31/702 ,  A61K31/715 ,  A61K47/54 ,  A61K49/00 ,  A61K47/64 ,  A61K47/42

Abstract: An object of the present invention is to provide an albumin-sugar chain complex bound with a number of sugar chains sufficient for obtaining a sugar chain clustering effect while also being able to exist comparatively stably in the body. The present invention provides an albumin-sugar chain complex having five or more molecules of an asparagine-linked sugar chain bound per molecule of albumin; a carrier for selectively delivering a functional molecule to a target tissue in the body that contains the aforementioned albumin-sugar chain complex; and a bioimaging probe having the aforementioned albumin-sugar chain complex as an active ingredient thereof that is administered into the body of an animal.

公开(公告)号：US09127041B2

公开(公告)日：2015-09-08

申请号：US14162642

申请日：2014-01-23

Applicant: Glytech, Inc.

Inventor： Yasuhiro Kajihara ,  Ryo Okamoto ,  Izumi Sakamoto ,  Kazuyuki Ishii

IPC: A61K38/00 ,  C07K2/00 ,  C07K4/00 ,  C07K5/00 ,  C07K7/00 ,  C07K14/00 ,  C07K16/00 ,  C07K17/00 ,  C07K1/107

CPC classification number: C07K1/1077 ,  C07K1/1072

Abstract: A process for chemically converting a peptide chain into a peptide thioester includes, when a —C(═X)—R1 group 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: —NH—C(═Y)NHR3 in an organic solvent, the —NH—C(═Y)NHR3 group 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 —NH—C(═Y)NHR3 group 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 —NH—C(═Y)NHR3 group has bound, whereby the —NH—C(═Y)NHR3 group is eliminated.

Abstract translation: 将肽链化学转化为肽硫酯的方法包括当将-C（= X）-R1基团引入半胱氨酸残基的硫醇基团时，然后将所得肽与具有离去基团的化合物反应 通过-NH-C（= Y）NHR 3在有机溶剂中，-NH-C（= Y）NHR 3基团通过加成反应与半胱氨酸残基的N-末端侧肽键的羧基结合 ，由此肽键被切割并且C末端侧肽片段被切断。 此外，当所得的具有-NH-C（= Y）NHR 3基团的肽链与缓冲溶液中的硫醇反应时，发生巯基交换反应，即硫醇的硫醇基与羰基碳结合， -NH-C（= Y）NHR 3基团结合，从而消除-NH-C（= Y）NHR 3基团。

公开(公告)号：US20130345129A1

公开(公告)日：2013-12-26

申请号：US13912625

申请日：2013-06-07

Applicant: Glytech, Inc.

Inventor： YASUHIRO KAJIHARA ,  TAKASHI TSUJI ,  IZUMI SAKAMOTO ,  YURI NAMBU ,  KAZUHIRO FUKAE ,  KATSUNARI TEZUKA ,  HIROAKI ASAI

IPC: C07K14/605

CPC classification number: C07K14/605 ,  A61K38/00

Abstract: 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.

公开(公告)号：US08569524B2

公开(公告)日：2013-10-29

申请号：US12529500

申请日：2008-02-28

Applicant: Mugio Nishizawa ,  Yoshiyasu Fukuyama ,  Hiroshi Imagawa

Inventor： Mugio Nishizawa ,  Yoshiyasu Fukuyama ,  Hiroshi Imagawa

IPC: C07D493/00

CPC classification number: C07D493/10

Abstract: The present invention provides a new bis(tetrahydrofuran) compound having an excellent neurotrophic factor activity-enhancing effect, and a process for producing the same. The bis(tetrahydrofuran) compound of the present invention is represented by formula (1): wherein R1 and R2 are the same or different, and represent a C1-4 alkyl group, a C1-5 alkoxy group, an aryl C1-5 alkoxy group, a C2-5 alkenyloxy group, or an aryl C2-5 alkenyloxy group, or R1 and R2 together represent ═O or ═CH2; R3 represents a hydrogen atom or a group —CH2—O—R4; R4 represents a C1-4 alkyl group, a C1-5 alkylcarbonyl group, or an aryl C1-4 alkyl group that may have a substituent on an aryl ring; and a carbon-carbon bond between “a” and “b” represents a single bond or a double bond. The bis(tetrahydrofuran) compound has an excellent neurotrophic factor activity-enhancing effect.

Abstract translation: 本发明提供了具有优异的神经营养因子活性增强作用的新的双（四氢呋喃）化合物及其制造方法。 本发明的双（四氢呋喃）化合物由式（1）表示：其中R1和R2相同或不同，表示C1-4烷基，C1-5烷氧基，芳基C1-5烷氧基 基团，C2-5烯氧基或芳基C2-5烯氧基，或R1和R2一起表示= O或= CH 2; R3表示氢原子或基团-CH2-O-R4; R4表示可以在芳基环上具有取代基的C1-4烷基，C1-5烷基羰基或芳基C1-4烷基; “a”和“b”之间的碳 - 碳键表示单键或双键。 双（四氢呋喃）化合物具有优异的神经营养因子活性增强作用。

公开(公告)号：US10047042B2

公开(公告)日：2018-08-14

申请号：US15030970

申请日：2014-10-22

Applicant: Glytech, Inc.

Inventor： Yasuhiro Kajihara ,  Yasuhito Morishita ,  Takefumi Murase

IPC: C12P13/22 ,  C12P13/02 ,  C12N9/10 ,  C07C319/28 ,  C07B57/00 ,  C12P41/00 ,  C07C319/02 ,  C07H21/04 ,  C12N9/80

Abstract: 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 β-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.

公开(公告)号：US20180186859A1

公开(公告)日：2018-07-05

申请号：US15740511

申请日：2016-06-30

Applicant: Glytech, Inc. ,  RIKEN

Inventor： Katsunori Tanaka ,  Yasuyoshi Watanabe ,  Akihiro Ogura ,  Takahiro Yamamoto

IPC: C07K14/765 ,  A61K47/42 ,  A61K49/00 ,  A61K31/702 ,  A61K31/715

Abstract: An object of the present invention is to provide an albumin-sugar chain complex bound with a number of sugar chains sufficient for obtaining a sugar chain clustering effect while also being able to exist comparatively stably in the body. The present invention provides an albumin-sugar chain complex having five or more molecules of an asparagine-linked sugar chain bound per molecule of albumin; a carrier for selectively delivering a functional molecule to a target tissue in the body that contains the aforementioned albumin-sugar chain complex; and a bioimaging probe having the aforementioned albumin-sugar chain complex as an active ingredient thereof that is administered into the body of an animal.

公开(公告)号：US09441024B2

公开(公告)日：2016-09-13

申请号：US14342360

申请日：2012-09-03

Applicant: Hirofumi Ochiai ,  Taiji Shimoda ,  Kazuhiro Fukae ,  Masatoshi Maeda ,  Keisuke Tazuru ,  Kenta Yoshida

Inventor： Hirofumi Ochiai ,  Taiji Shimoda ,  Kazuhiro Fukae ,  Masatoshi Maeda ,  Keisuke Tazuru ,  Kenta Yoshida

IPC: A61K38/31 ,  A61P5/02 ,  C07K14/655 ,  C07K14/47 ,  A61K47/48 ,  A61K38/00

CPC classification number: C07K14/655 ,  A61K38/00 ,  A61K47/549 ,  C07K14/47 ,  C07K14/6555

Abstract: [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.

Abstract translation: 提供对生长抑素受体具有亲和力的糖基化多肽，与生长激素类似物具有改善的血液内稳定性。 [溶液]糖基化多肽的特征在于生长抑素中的至少两个氨基酸或其类似物被糖基化的氨基酸替代。

公开(公告)号：US09073978B2

公开(公告)日：2015-07-07

申请号：US14004122

申请日：2012-03-05

Applicant: Yasuhiro Kajihara ,  Masumi Murakami ,  Kazuyuki Ishii

Inventor： Yasuhiro Kajihara ,  Masumi Murakami ,  Kazuyuki Ishii

IPC: C07H1/00 ,  C07K1/06 ,  C07K14/00 ,  C07K1/00

CPC classification number: C07K14/001 ,  C07H1/00 ,  C07K1/006 ,  C07K1/068

Abstract: [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.

Abstract translation: 技术问题提供一种制造方法，当通过Boc固相合成方法合成糖肽时，能够以高产率获得含有唾液酸糖链的目标糖肽，而不会在糖链的非还原末端分解唾液酸 。 [问题的解决方案]本发明的特征在于Boc固相合成法中使用的Boc-唾液酸糖基化氨基酸衍生物，其中在糖链非还原末端的唾液酸的羧基被苯甲酰基保护 。