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公开(公告)号:US20240117402A1
公开(公告)日:2024-04-11
申请号:US18264843
申请日:2022-02-10
Applicant: Nanyang Technological University
Inventor: Chuan Fa Liu , Dingpeng Zhang , Zhen Wang , James P. Tam
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.
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公开(公告)号:US20180274003A1
公开(公告)日:2018-09-27
申请号:US15765156
申请日:2016-09-29
Applicant: Nanyang Technological University
Inventor: James P Tam , Kien Truc Giang Nguyen , Yuan Cao , Chuan Fa Liu
CPC classification number: C12P21/02 , A61K38/00 , C07K1/02 , C07K5/1019 , C07K7/06 , C07K11/00 , C12N9/63 , C12N9/93
Abstract: The present invention relates to a method of forming a peptide of Formula (I) (P1-Xaa1-Xaa2-P2) by ligating a first peptide of Formula (II) (P1-Xaa1-X—R, wherein X is O or S) to a second peptide of Formula (II I) (Xaa1-Xaa2-P2) by enzymatically cleaving the bond between “Asx” and “X” in the first peptide of Formula (II) and ligating the fragment P1-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.
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3.
公开(公告)号:US09453044B2
公开(公告)日:2016-09-27
申请号:US14376675
申请日:2013-02-06
Applicant: NANYANG TECHNOLOGICAL UNIVERSITY
Inventor: Chuan Fa Liu , Junfeng Zhao
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。
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公开(公告)号:US11091786B2
公开(公告)日:2021-08-17
申请号:US15765156
申请日:2016-09-29
Applicant: Nanyang Technological University
Inventor: James P Tam , Kien Truc Giang Nguyen , Yuan Cao , Chuan Fa Liu
Abstract: The present invention relates to a method of forming a peptide of Formula (I) (P1-Xaa1-Xaa2-P2) by ligating a first peptide of Formula (II) (P1-Xaa1-X—R, wherein X is O or S) to a second peptide of Formula (III) (Xaa1-Xaa2-P2) by enzymatically cleaving the bond between “Asx” and “X” in the first peptide of Formula (II) and ligating the fragment P1-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.
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公开(公告)号:US20240263210A1
公开(公告)日:2024-08-08
申请号:US18465824
申请日:2023-09-12
Applicant: Nanyang Technological University
Inventor: Bin Wu , Renliang Yang , Yee Hwa Wong , Julien Lescar , Chuan Fa Liu , James P Tam , Kien Truc Giang Nguyen , Ziqi Long
IPC: C12P21/02 , C07K14/415 , C12N9/00
CPC classification number: C12P21/02 , C07K14/415 , C12N9/93
Abstract: The present invention relates to identification and utilization of a novel structural feature governing efficient peptide ligation of OaAEP1 and a method of forming a peptide of Formula (I) by ligating a first peptide of Formula (II) to a second peptide of Formula (III) by enzymatically cleaving the bond between “Asx” and “Xaa3” in the first peptide of Formula (II) and ligating the fragment P1-Asx of the first peptide via its C-terminus to the N-terminus of the second peptide of Formula (III) to form a ligated peptide of Formula (I), wherein the enzymatic cleavage and ligation reaction is catalyzed by a peptide ligase having the activity of OaAEP1 Cys247Ala (SEQ ID NO:1) under conditions suitable for said cleavage and ligation reaction. 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 catalyzed by the peptide ligase having the activity of OaAEP1 Cys247Ala (SEQ ID NO:1). Also encompassed in the invention are the ligated peptides and/or tagged target cells obtainable according to any of the methods of the invention, the peptide ligase OaAEP1 Cys247Ala having the amino acid sequence of SEQ ID NO:1 and other peptide ligases having the activity thereof, as well as kits comprising any of said peptide ligases, in particular OaAEP1 Cys247Ala (SEQ ID NO:1).
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公开(公告)号:US11795488B2
公开(公告)日:2023-10-24
申请号:US16336023
申请日:2017-09-12
Applicant: NANYANG TECHNOLOGICAL UNIVERSITY
Inventor: Bin Wu , Renliang Yang , Yee Hwa Wong , Julien Lescar , Chuan Fa Liu , James P Tam , Kien Truc Giang Nguyen , Ziqi Long
IPC: C12P21/02 , C12N9/00 , C07K14/415
CPC classification number: C12P21/02 , C07K14/415 , C12N9/93
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.
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7.
公开(公告)号:US20150344519A1
公开(公告)日:2015-12-03
申请号:US14376675
申请日:2013-02-06
Applicant: NANYANG TECHNOLOGICAL UNIVERSITY
Inventor: Chuan Fa Liu , Junfeng Zhao
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。
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