Synthesis of Disulfide Surrogate Peptides Incorporating Large-Span Surrogate Bridges Through a Native-Chemical-Ligation-Assisted Diaminodiacid Strategy

doi:10.1002/anie.201915358

	Synthesis of Disulfide Surrogate Peptides Incorporating Large-Span Surrogate Bridges Through a Native-Chemical-Ligation-Assisted Diaminodiacid Strategy
	Qu, Qian 1; Gao, Shuai 1; Wu, Fangming 2; Zhang, Meng-Ge 3; Li, Ying 3; Zhang, Long-Hua 3; Bierer, Donald 4; Tian, Chang-Lin 2,3; Zheng, Ji-Shen 3; Liu, Lei 1
刊名	ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
	2020-04-06
卷号	59
关键词	chemical protein synthesis cyclic peptides disulfides native chemical ligation peptides
ISSN号	1433-7851
DOI	10.1002/anie.201915358
通讯作者	Tian, Chang-Lin(cltian@ustc.edu.cn) ; Zheng, Ji-Shen(jszheng@ustc.edu.cn) ; Liu, Lei(lliu@mail.tsinghua.edu.cn)
英文摘要	The use of synthetic bridges as surrogates for disulfide bonds has emerged as a practical strategy to obviate the poor stability of some disulfide-containing peptides. However, peptides incorporating large-span synthetic bridges are still beyond the reach of existing methods. Herein, we report a native chemical ligation (NCL)-assisted diaminodiacid (DADA) strategy that enables the robust generation of disulfide surrogate peptides incorporating surrogate bridges up to 50 amino acids in length. This strategy provides access to some highly desirable but otherwise impossible-to-obtain disulfide surrogates of bioactive peptide. The bioactivities and structures of the synthetic disulfide surrogates were verified by voltage clamp assays, NMR, and X-ray crystallography; and stability studies established that the disulfide replacements effectively overcame the problems of disulfide reduction and scrambling that often plague these pharmacologically important peptides.
资助项目	National Key R&D Program of China[2017YFA0505200] ; National Key R&D Program of China[2019YFA0706902] ; NSFC[21532004] ; NSFC[91753205] ; NSFC[81621002] ; NSFC[U1732161] ; NSFC[91753120] ; NSFC[21825703] ; NSFC[U1732275] ; NSFC[21927814] ; CAS[XDB08030302] ; Science and Technological Fund of Anhui Province for Outstanding Youth[1808085J04] ; High Magnetic Field Laboratory of Anhui Province
WOS关键词	SOLID-PHASE SYNTHESIS ; ALPHA-CONOTOXIN ; CYCLIC-PEPTIDES ; PROTEINS ; ANALOGS ; DISCOVERY ; CYSTEINE ; TOXIN ; IMI
WOS研究方向	Chemistry
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000519963000001
资助机构	National Key R&D Program of China ; NSFC ; CAS ; Science and Technological Fund of Anhui Province for Outstanding Youth ; High Magnetic Field Laboratory of Anhui Province
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/103801]
专题	中国科学院合肥物质科学研究院
通讯作者	Tian, Chang-Lin; Zheng, Ji-Shen; Liu, Lei
作者单位	1.Tsinghua Univ, Key Lab Bioorgan Phosphorus Chem & Chem Biol, Ctr Synthet & Syst Biol,Dept Chem, Tsinghua Peking Ctr Life Sci,Minist Educ, Beijing 100084, Peoples R China 2.Chinese Acad Sci, High Field Magnet Lab, Hefei 230031, Peoples R China 3.Univ Sci & Technol China, Sch Life Sci, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Peoples R China 4.Bayer AG, Dept Med Chem, Aprather Weg 18A, D-42096 Wuppertal, Germany
推荐引用方式 GB/T 7714	Qu, Qian,Gao, Shuai,Wu, Fangming,et al. Synthesis of Disulfide Surrogate Peptides Incorporating Large-Span Surrogate Bridges Through a Native-Chemical-Ligation-Assisted Diaminodiacid Strategy[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2020,59.
APA	Qu, Qian.,Gao, Shuai.,Wu, Fangming.,Zhang, Meng-Ge.,Li, Ying.,...&Liu, Lei.(2020).Synthesis of Disulfide Surrogate Peptides Incorporating Large-Span Surrogate Bridges Through a Native-Chemical-Ligation-Assisted Diaminodiacid Strategy.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,59.
MLA	Qu, Qian,et al."Synthesis of Disulfide Surrogate Peptides Incorporating Large-Span Surrogate Bridges Through a Native-Chemical-Ligation-Assisted Diaminodiacid Strategy".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 59(2020).