公开(公告)号：WO2022186782A1

公开(公告)日：2022-09-09

申请号：PCT/SG2022/050117

申请日：2022-03-07

Applicant: NANYANG TECHNOLOGICAL UNIVERSITY

Inventor： LIU, Chuan Fa ,  XIA, Yiyin ,  TAM, James P.

IPC: C12P21/04 ,  C07K7/64 ,  C07K14/00 ,  A61K38/12 ,  A61K38/16

Abstract: The present invention relates to methods that employ enzymes having Asn-specific cyclase activity as a means for generating cyclic (poly)peptides from (poly)peptides that comprise a ligation motif comprising a Nγ-hydroxy-L-asparagine or Nγ-amino-L-asparagine residue. Further encompassed are the resulting cyclic (poly)peptides and the corresponding uses.

公开(公告)号：WO2010027326A1

公开(公告)日：2010-03-11

申请号：PCT/SG2008/000324

申请日：2008-09-03

Applicant: NANYANG TECHNOLOGICAL UNIVERSITY ,  LIU, Chuan Fa ,  ZENG, Yun ,  LU, Xiao Wei

Inventor： LIU, Chuan Fa ,  ZENG, Yun ,  LU, Xiao Wei

IPC: C07D239/557 ,  C07D473/18 ,  C07D239/60 ,  C07D473/34

CPC classification number: C07D239/557 ,  C07D239/60 ,  C07D473/18 ,  C07D473/34 ,  C07K14/003

Abstract: Disclosed is a peptide nucleic acid monomer as well as a corresponding peptide nucleic acid molecule. The monomer comprises a terminal amino group and a terminal group A. The terminal amino group and the terminal group A are connected by an aliphatic moiety. T he main chain of this aliphatic moiety is free of groups that are charged under physiological conditions. The terminal group A is one of -COOH, -COOR 3 , -COX, -COSR 3 , -CN, -CONH 2 , -CONHR 3 , -CONR 3 , R 4 , with R 3 and R4 being H or an aliphatic, alicyclic, aromatic, a rylaliphatic or arylalicyclic group, and X being a halogen atom. The terminal amino group is substituted by an aliphatic group wit h a main chain of at least two carbon atoms and optionally 0 to a bout 2 heteroatoms selected from the group N, O, S, Se and Si. Th e main chain has a polar head group Z.

Abstract translation: 公开了肽核酸单体以及相应的肽核酸分子。 单体包括末端氨基和末端基团A.末端氨基和末端基团A通过脂肪族部分连接。 该脂肪族部分的主链不含在生理条件下带电的基团。 末端基团A是-COOH，-COOR 3，-COX，-COSR 3，-CN，-CONH 2，-CONHR 3，-CONR 3，R 4中的一个，其中R 3和R 4是H或脂族，脂环族，芳族，脂族基或 芳基脂环基，X为卤素原子。 末端氨基被具有至少两个碳原子的主链的任选的脂族基团取代，并且任选地与选自N，O，S，Se和Si的2个杂原子取代。 主链有极性头组Z。

公开(公告)号：WO2013119184A1

公开(公告)日：2013-08-15

申请号：PCT/SG2013/000052

申请日：2013-02-06

Applicant: NANYANG TECHNOLOGICAL UNIVERSITY

Inventor： LIU, Chuan Fa ,  ZHAO, Junfeng

IPC: C07K1/107 ,  C07K1/02 ,  C07K2/00 ,  C07D273/04

CPC classification number: C07K1/10 ,  C07K1/02 ,  C07K1/026 ,  C07K1/04 ,  C07K7/64

Abstract: The invention relates to the synthesis of peptides, proteins and related bioconjugates, and in particular, to such synthesis using a peptide ligation method whereby a C-terminal salicylaldehyde ester peptide is reacted with an aminoacyl-N-hydroxl peptide. The invention also relates to the synthesis of cyclic peptides, including serinyl- or threonyl-containing cyclic peptides. The invention further relates to a solid phase synthesis of C-terminal salicylaldehyde ester peptides.

Abstract translation: 本发明涉及肽，蛋白质和相关生物缀合物的合成，特别涉及使用C-末端水杨醛酯肽与氨基酰基-N-羟基肽反应的肽连接方法的这种合成。 本发明还涉及环肽的合成，包括含有丝氨酰基或苏氨酰的环肽。 本发明还涉及C-末端水杨醛酯肽的固相合成。

公开(公告)号：WO2022173377A1

公开(公告)日：2022-08-18

申请号：PCT/SG2022/050069

申请日：2022-02-10

Applicant: NANYANG TECHNOLOGICAL UNIVERSITY

Inventor： LIU, Chuan Fa ,  ZHANG, Dingpeng ,  WANG, Zhen ,  TAM, James P.

IPC: C12P21/02 ,  C07K19/00

Abstract: The present invention relates to methods that employ enzymes having Asx-specific ligase and cyclase activity, namely butelase-1, VyPAL2 and OaAEPI b, as a means for engineering novel (poly) peptide theranostics. The differential substrate specificities and differential optimal pH of the Asx-specific ligase and cyclase are used to provide sufficient orthogonality for a tandem ligation and cyclization of proteins. Also encompassed are the corresponding uses.

公开(公告)号：WO2018056899A1

公开(公告)日：2018-03-29

申请号：PCT/SG2017/050458

申请日：2017-09-12

Applicant: NANYANG TECHNOLOGICAL UNIVERSITY

Inventor： WU, Bin ,  YANG, Renliang ,  WONG, Yee Hwa ,  LESCAR, Julien ,  LIU, Chuan Fa ,  TAM, James P ,  NGUYEN, Kien Truc Giang ,  LONG, Ziqi

IPC: C07K14/415 ,  C12N9/00 ,  C12P21/04

Abstract: The present invention relates to a method of ligating a first peptide via its C-terminus to the N-terminus of a second peptide, wherein the reaction is catalyzed by an asparagine/aspartate (Asx) peptide ligase OaAEPI Cys247Ala having the amino acid sequence of SEQ ID NO: 1. Further encompassed are a method of preparing a dimer, oligomer, or multimer of one or more peptides of interest and a method of modifying or tagging the surface of a target cell by one or more peptides of interest. Also encompassed in the invention are the ligated peptides and/or tagged target cells obtainable according to any of the methods, the peptide ligase OaAEPI Cys247Ala having the amino acid sequence of SEQ ID NO: 1, as well as kits comprising said peptide ligase.

Abstract translation: 本发明涉及将第一肽经由其C端连接至第二肽的N端的方法，其中所述反应由天冬酰胺/天冬氨酸（Asx）肽连接酶 OaAEPI Cys247Ala具有SEQ ID NO：1的氨基酸序列。进一步包括制备一种或多种感兴趣的肽的二聚体，寡聚体或多聚体的方法，以及将靶细胞表面修饰或标记一个 或更多感兴趣的肽。 本发明还包括根据任何方法可获得的连接的肽和/或标记的靶细胞，具有SEQ ID NO：1的氨基酸序列的肽连接酶OaAEPI Cys247Ala，以及包含所述肽连接酶的试剂盒。 / p>

公开(公告)号：WO2017058114A1

公开(公告)日：2017-04-06

申请号：PCT/SG2016/050481

申请日：2016-09-29

Applicant: NANYANG TECHNOLOGICAL UNIVERSITY

Inventor： TAM, James P ,  NGUYEN, Kien Truc Giang ,  CAO, Yuan ,  LIU, Chuan Fa

IPC: C07K11/00 ,  C12N9/50 ,  A61K38/02

CPC classification number: C07K1/02 ,  A61K38/00 ,  C07K5/1019 ,  C07K7/06 ,  C07K11/00 ,  C12N9/63 ,  C12N9/93 ,  C12P21/02

Abstract: The present invention relates to a method of forming a peptide of Formula (I) (P 1 -Xaa 1 -Xaa 2 -P 2 ) by ligating a first peptide of Formula (II) (P 1 -Xaa 1 -X-R, wherein X is O or S) to a second peptide of Formula (II I) (Xaa 1 -Xaa 2 -P 2 ) by enzymatically cleaving the bond between "Asx" and "X" in the first peptide of Formula (II) and ligating the fragment P 1 -Asx of the first peptide to the second peptide of Formula (III), wherein the enzymatic cleavage and ligation reaction is catalyzed by butelase 1 (SEQ ID NO: 1 ) and the peptide of Formula (I) is a depsipeptide, preferably a thiodepsipeptide. Further encompassed are peptides and dendrimeric peptide assemblies prepared using the presently disclosed method, as well as use of the dendrimeric peptide assemblies as a vaccine, medicament, or diagnostic agent, particularly as an antimicrobial agent.

Abstract translation: 本发明涉及通过将式（II）的第一肽（P1-Xaa1-XR，其中X为O或S）连接到第（II-Xaa1-Xaa2-P2）的肽而形成式 通过在式（II）的第一肽中酶切割“Asx”和“X”之间的键并将第一肽的片段P1-Asx连接到第一肽的第二个肽（IIa）的第二个肽（Xaa1-Xaa2-P2） 式（III）的第二肽，其中酶切割和连接反应由丁内酯酶1（SEQ ID NO：1）催化，式（I）的肽是去肽肽，优选硫代三肽。 进一步包括使用本公开的方法制备的肽和树状聚合肽组件，以及使用树状聚合肽组合物作为疫苗，药物或诊断剂，特别是作为抗微生物剂。

公开(公告)号：WO2012005691A1

公开(公告)日：2012-01-12

申请号：PCT/SG2011/000236

申请日：2011-07-06

Applicant: NANYANG TECHNOLOGICAL UNIVERSITY ,  LIU, Chuan Fa

Inventor： LIU, Chuan Fa

IPC: C07C323/60 ,  C07K1/06 ,  C07K1/04

CPC classification number: C07K1/1077 ,  C07C323/29 ,  C07K1/04 ,  C07K1/086

Abstract: The present invention generally relates to processes and methods of peptide and protein synthesis. The present invention also relates to specific compounds for use in such processes and methods. It is shown herein that peptides with a C-terminal tertiary N,N -bis(2-mercaptoethyl)-amide (BMEA) undergo N -to- S acyl transfer at weakly acidic pH to form a transient thioester which can be captured for direct ligation with a cysteinyl peptide. These C-terminal BMEA peptides are easily prepared with standard Fmoc solid-phase synthesis protocols, thus giving a very convenient access to the thioester components for native chemical ligation.

Abstract translation: 本发明一般涉及肽和蛋白质合成的方法和方法。 本发明还涉及用于这些方法和方法的具体化合物。 在本文中显示，具有C末端叔N，N-双（2-巯基乙基） - 酰胺（BMEA）的肽在弱酸性pH下经历N-to-S酰基转移以形成瞬时硫酯，其可捕获直接 与半胱氨酰肽连接。 这些C-末端BMEA肽可以用标准的Fmoc固相合成方案容易地制备，从而使得非常方便地获得用于天然化学连接的硫酯组分。