公开(公告)号：US10077447B2

公开(公告)日：2018-09-18

申请号：US14924201

申请日：2015-10-27

Applicant: AJINOMOTO CO., INC.

Inventor： Sergey Vasilievich Smirnov ,  Veronika Aleksandrovna Kotliarova ,  Hidemi Fujii ,  Masakazu Sugiyama

IPC: C12N15/77 ,  C07K14/605 ,  C07K1/107 ,  C07K16/32 ,  C07K14/34 ,  C12P21/02 ,  C12P21/06 ,  C12N15/62 ,  C07K1/00

CPC classification number: C12N15/77 ,  C07K1/003 ,  C07K1/107 ,  C07K14/34 ,  C07K14/605 ,  C07K16/32 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/20 ,  C07K2319/21 ,  C07K2319/30 ,  C07K2319/92 ,  C12N15/62 ,  C12P21/02 ,  C12P21/06

Abstract: The present invention provides a coryneform bacterium having an ability to produce a heterologous fusion protein by secretory production, which has been modified to express a genetic construct for secretory production of the heterologous fusion protein encoding at least a heterologous fusion protein comprising an extein and an intein having an activity of acyl rearrangement. The method for producing proteins modified at the C-terminus is also provided.

公开(公告)号：US10072041B2

公开(公告)日：2018-09-11

申请号：US13985369

申请日：2012-02-15

Applicant: Oleg Melnyk ,  Nathalie Ollivier ,  Reda Mhidia ,  Julien Dheur

Inventor： Oleg Melnyk ,  Nathalie Ollivier ,  Reda Mhidia ,  Julien Dheur

IPC: C07K1/26 ,  C07K1/02 ,  C07K1/00

CPC classification number: C07K1/026 ,  C07K1/003

Abstract: Method for preparing a peptide assembly of n fragments and n−1 amino acids bearing a thiol function, represented by the formula: A1-C1-A2-C2-A3- . . . -Ci−1-Ai- . . . -Cn−1-An  (I) in which A1, A2, A3, . . . Ai . . . , An are peptide fragments, C1, C2, C3 . . . Ci−1 . . . Cn−1 are amino acid residues bearing a thiol function, n is comprised between 3 and 50, and i is 2 to n, in which a peptide-thioester is prepared of formula: A1-SR (II) in which A1 is a peptide fragment and SR is an alkyl thioester residue, R being alkyl optionally substituted, starting from a bis(2-sulphanylethyl)amino peptide.

公开(公告)号：US10053491B2

公开(公告)日：2018-08-21

申请号：US15146589

申请日：2016-05-04

Applicant: AJINOMOTO CO., INC.

Inventor： Akira Otaka ,  Akira Shigenaga ,  Masakazu Sugiyama ,  Hidemi Fujii

IPC: C07K1/107 ,  C07K7/06 ,  C07K1/13 ,  C07K1/00 ,  C07D249/00

CPC classification number: C07K7/06 ,  C07D249/00 ,  C07K1/003 ,  C07K1/107 ,  C07K1/13

Abstract: An object of the present invention is to provide a method for producing a peptide thioester compound, a peptide hydrazide compound, and a peptide amide compound. The present invention provides a method for producing a peptide hydrazide compound or a peptide amide compound by using a compound represented by Formula (2): wherein R1, R2, R3, and X are as defined in the specification, and using a hydrazine compound or an ammonia compound as a reaction reagent. The present invention also provides a method for producing a peptide thioester compound from the peptide hydrazide compound.

公开(公告)号：US20160264626A1

公开(公告)日：2016-09-15

申请号：US15146589

申请日：2016-05-04

Applicant: AJINOMOTO CO., INC.

Inventor： Akira OTAKA ,  Akira Shigenaga ,  Masakazu Sugiyama ,  Hidemi Fujii

IPC: C07K7/06 ,  C07D249/00

CPC classification number: C07K7/06 ,  C07D249/00 ,  C07K1/003 ,  C07K1/107 ,  C07K1/13

Abstract: An object of the present invention is to provide a method for producing a peptide thioester compound, a peptide hydrazide compound, and a peptide amide compound. The present invention provides a method for producing a peptide hydrazide compound or a peptide amide compound by using a compound represented by Formula (2): wherein R1, R2, R3, and X are as defined in the specification, and using a hydrazine compound or an ammonia compound as a reaction reagent. The present invention also provides a method for producing a peptide thioester compound from the peptide hydrazide compound.

Abstract translation: 其中R1，R2，R3和X如说明书中所定义，并且使用肼化合物或氨化合物作为反应试剂。 本发明还提供了从肽酰肼化合物制备肽硫酯化合物的方法。

公开(公告)号：US20160060640A1

公开(公告)日：2016-03-03

申请号：US14924201

申请日：2015-10-27

Applicant: AJINOMOTO CO., INC.

Inventor： Sergey Vasilievich Smirnov ,  Veronika Aleksandrovna Kotliarova ,  Hidemi Fujii ,  Masakazu Sugiyama

IPC: C12N15/77 ,  C07K14/605 ,  C07K16/32 ,  C12N15/62

CPC classification number: C12N15/77 ,  C07K1/003 ,  C07K1/107 ,  C07K14/34 ,  C07K14/605 ,  C07K16/32 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/20 ,  C07K2319/21 ,  C07K2319/30 ,  C07K2319/92 ,  C12N15/62 ,  C12P21/02 ,  C12P21/06

Abstract: The present invention provides a coryneform bacterium having an ability to produce a heterologous fusion protein by secretory production, which has been modified to express a genetic construct for secretory production of the heterologous fusion protein encoding at least a heterologous fusion protein comprising an extein and an intein having an activity of acyl rearrangement. The method for producing proteins modified at the C-terminus is also provided.

Abstract translation: 本发明提供了具有通过分泌生产产生异源融合蛋白的能力的棒状细菌，其已被修饰以表达用于分泌编码至少包含外显子和内含肽的异源融合蛋白的异源融合蛋白的遗传构建体 具有酰基重排活性。 还提供了在C末端修饰的蛋白质的制备方法。

公开(公告)号：US20150315129A1

公开(公告)日：2015-11-05

申请号：US14583850

申请日：2014-12-29

Applicant: EMORY UNIVERSITY

Inventor： Lanny S. Liebeskind ,  Wenting Wu ,  Zhihui Zhang ,  Hao Li ,  Angus A. Lamar

IPC: C07C231/02 ,  C07C233/69 ,  C07C233/07 ,  C07D307/52 ,  C07D295/192 ,  C07D233/90 ,  C07C233/65 ,  C07D213/82

CPC classification number: C07C231/02 ,  C07C233/07 ,  C07C233/65 ,  C07C233/69 ,  C07D213/82 ,  C07D233/90 ,  C07D295/192 ,  C07D307/52 ,  C07F7/1804 ,  C07H1/00 ,  C07H21/02 ,  C07K1/003 ,  C07K1/02 ,  C07K5/06026 ,  C07K5/06034 ,  C07K5/0606 ,  C07K5/06078 ,  C07K5/06086 ,  C07K5/06104 ,  C07K5/0812

Abstract: The disclosure relates to methods for producing amide bonds and reagents related thereto. In some embodiments, the disclosure relates to methods of producing an amide comprising mixing an O-silylated thionoester and an amine under conditions such that an amide is formed. In another embodiment, the disclosure relates to mixing a thiolacid, a silylating agent, and an amine under conditions such that an amide is formed.

Abstract translation: 本公开涉及制备酰胺键的方法和与其相关的试剂。 在一些实施方案中，本公开涉及制备酰胺的方法，包括在形成酰胺的条件下混合O-甲硅烷基化的硫代酯和胺。 在另一个实施方案中，本公开涉及在形成酰胺的条件下混合硫醇酸，甲硅烷基化试剂和胺。

公开(公告)号：US08921599B2

公开(公告)日：2014-12-30

申请号：US13280991

申请日：2011-10-25

Applicant: Lanny S. Liebeskind ,  Wenting Wu ,  Zhihui Zhang ,  Hao Li ,  Angus A. Lamar

Inventor： Lanny S. Liebeskind ,  Wenting Wu ,  Zhihui Zhang ,  Hao Li ,  Angus A. Lamar

IPC: C07C211/08 ,  C07H1/00 ,  C07D213/82 ,  C07D233/90 ,  C07D295/192 ,  C07D307/52 ,  C07F7/18 ,  C07H21/02 ,  C07K1/00 ,  C07K1/02 ,  C07K5/062 ,  C07K5/065 ,  C07K5/068 ,  C07K5/072 ,  C07K5/087

CPC classification number: C07C231/02 ,  C07C233/07 ,  C07C233/65 ,  C07C233/69 ,  C07D213/82 ,  C07D233/90 ,  C07D295/192 ,  C07D307/52 ,  C07F7/1804 ,  C07H1/00 ,  C07H21/02 ,  C07K1/003 ,  C07K1/02 ,  C07K5/06026 ,  C07K5/06034 ,  C07K5/0606 ,  C07K5/06078 ,  C07K5/06086 ,  C07K5/06104 ,  C07K5/0812

Abstract: The disclosure relates to methods for producing amide bonds and reagents related thereto. In some embodiments, the disclosure relates to methods of producing an amide comprising mixing an O-silylated thionoester and an amine under conditions such that an amide is formed. In another embodiment, the disclosure relates to mixing a thiolacid, a silylating agent, and an amine under conditions such that an amide is formed.

Abstract translation: 本公开涉及制备酰胺键的方法和与其相关的试剂。 在一些实施方案中，本公开涉及制备酰胺的方法，包括在形成酰胺的条件下混合O-甲硅烷基化的硫代酯和胺。 在另一个实施方案中，本公开涉及在形成酰胺的条件下混合硫醇酸，甲硅烷基化试剂和胺。

公开(公告)号：US20140058070A1

公开(公告)日：2014-02-27

申请号：US13822821

申请日：2011-09-08

Applicant: Chengzao Sun ,  Behrouz Bruce Forood ,  Gary Luo ,  Soumitra S. Ghosh

Inventor： Chengzao Sun ,  Behrouz Bruce Forood ,  Gary Luo ,  Soumitra S. Ghosh

IPC: C07K1/00

CPC classification number: C07K1/003 ,  C07C211/27 ,  C07D311/88 ,  C07K1/107

Abstract: There are provided compounds and methods for amidating the C-terminus of a polypeptide. The method include reacting a polypeptide which includes a C-terminal thioester or C-terminal selenoester with any one of a defined set of auxiliary molecules under conditions suitable to produce a polypeptide adduct which includes the auxiliary molecule chemically bound at the C-terminal of the polypeptide. In the subsequent step, the auxiliary molecule is removed from the C-terminal of the polypeptide adduct under conditions suitable to produce an amidated polypeptide.

Abstract translation: 提供了用于酰胺化多肽的C末端的化合物和方法。 该方法包括在适于产生多肽加合物的条件下使包含C-末端硫酯或C-末端硒酸酯的多肽与定义的一组辅助分子中的任一个反应，所述多肽加合物包括在C末端化学结合的辅助分子 多肽。 在随后的步骤中，辅助分子在适于产生酰胺化多肽的条件下从多肽加合物的C-末端去除。

公开(公告)号：US08492503B2

公开(公告)日：2013-07-23

申请号：US13063720

申请日：2009-09-11

Applicant: Sean M. Culbertson ,  Xiaoming Shen ,  Antoni Kozlowski ,  Samuel P. McManus

Inventor： Sean M. Culbertson ,  Xiaoming Shen ,  Antoni Kozlowski ,  Samuel P. McManus

IPC: C08G12/04

CPC classification number: C08G65/2606 ,  A61K38/00 ,  A61K47/60 ,  C07K1/003 ,  C07K17/08 ,  C08G65/26 ,  C08G65/2609 ,  C08G65/331 ,  C08G65/3315 ,  C08G65/3318 ,  C08G65/3326 ,  C08G65/33306 ,  C08G65/33313 ,  C08G65/33317 ,  C08G65/33327 ,  C08L71/02

Abstract: Provided herein are polymeric α-hydroxy aldehyde or α-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the α-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

Abstract translation: 本文提供的是聚合的α-羟基醛或α-羟基酮试剂，其可以与含胺化合物缀合以在单步反应中形成稳定的共轭物。 在选择的实施方案中，聚合物试剂本身包含内部质子抽提（碱性）官能团，以促进更有效的反应。 如果需要，取代基通过接头适当地定位，以使基团定位用于质子抽取，优选在抽提原子和α-碳上的氢原子之间提供4或5键间距。 还提供了使用试剂和试剂的稳定的，溶解的缀合物与生物活性化合物的方法。 在优选的实施方案中，试剂或缀合物的聚合物组分是聚乙二醇。

公开(公告)号：US20080200648A1

公开(公告)日：2008-08-21

申请号：US11632448

申请日：2005-07-13

Applicant: Matthieu Giraud ,  Michaela Williner ,  Oleg Werbitzky

Inventor： Matthieu Giraud ,  Michaela Williner ,  Oleg Werbitzky

IPC: C07K1/107

CPC classification number: C07K7/08 ,  C07C231/02 ,  C07K1/003

Abstract: A novel for amidation of C-terminal carboxyl groups of peptides is devised, which methods avoids undesired epimerisation of the α-carbon of the C-terminal amino acid yielding diastereoisomeric variants of the amidated peptide.

Abstract translation: 设计了肽的C末端羧基酰胺化的一种新方法，该方法避免了产生酰胺化肽的非对映异构体变体的C端氨基酸的α-碳不希望的差向异构化。