Chemical synthesis and biological activity of peptides incorporating an ether bridge as a surrogate for a disulfide bond

doi:10.1039/d0sc02374d

	Chemical synthesis and biological activity of peptides incorporating an ether bridge as a surrogate for a disulfide bond
	Zhao, Rui 5,6; Shi, Pan 5; Chen, Junyou 6; Sun, Shuaishuai 6; Chen, Jingnan 6; Cui, Jibin 6; Wu, Fangming 4; Fang, Gemin 3; Tian, Changlin 5; Shi, Jing 5
刊名	CHEMICAL SCIENCE
	2020-08-14
卷号	11
ISSN号	2041-6520
DOI	10.1039/d0sc02374d
通讯作者	Shi, Jing(shijing@ustc.edu.cn) ; Li, Yi-Ming(ymli@hfut.edu.cn)
英文摘要	Disulfide bridges contribute to the definition and rigidity of polypeptides, but they are inherently unstable in reducing environments and in the presence of isomerases and nucleophiles. Strategies to address these deficiencies, ideally without significantly perturbing the structure of the polypeptide, would be of great interest. One possible surrogate for the disulfide bridge is a simple thioether, but these are susceptible to oxidation. We report the introduction of an ether linkage into the biologically active, disulfide-rich peptides oxytocin, tachyplesin I, and conotoxin alpha-ImI, using an ether-containing diaminodiacid as the key building block, obtained by the stereoselective ring-opening addition reaction of an aziridine skeleton with a hydroxy group. NMR studies indicated that the derivatives with an ether surrogate bridge exhibited very small change of their three-dimensional structures. The analogs obtained using this novel substitution strategy were found to be more stable than the original peptide in oxidative and reductive conditions; without a loss of bioactivity. This strategy is therefore proposed as a practical and versatile solution to the stability problems associated with cysteine-rich peptides.
资助项目	National Key R&D Program of China[2017YFA0505400] ; National Key R&D Program of China[2017YFA0505200] ; National Natural Science Foundation of China[91753205] ; National Natural Science Foundation of China[21877024] ; National Natural Science Foundation of China[21977089] ; National Natural Science Foundation of China[81621002] ; National Natural Science Foundation of China[31971152] ; National Natural Science Foundation of China[21621003] ; Fundamental Research Funds for the Central Universities[JZ2019HGPB0105]
WOS关键词	SOLID-PHASE SYNTHESIS ; ALPHA-CONOTOXIN ; EFFICIENT SYNTHESIS ; REPLACEMENT ; TACHYPLESIN ; AZIRIDINES ; HELICITY ; PROTEINS ; ANALOGS ; CYSTINE
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000555801800018
资助机构	National Key R&D Program of China ; National Natural Science Foundation of China ; Fundamental Research Funds for the Central Universities
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/44927]
专题	中国科学院合肥物质科学研究院
通讯作者	Shi, Jing; Li, Yi-Ming
作者单位	1.Tsinghua Univ, Dept Chem, Beijing 100084, Peoples R China 2.Bayer AG, Dept Med Chem, Aprather Weg 18A, D-4206 Wuppertal, Germany 3.Anhui Univ, Sch Life Sci, Inst Phys Sci & Informat Technol, Hefei 230601, Peoples R China 4.Chinese Acad Sci, High Magnet Field Lab, Hefei 230031, Peoples R China 5.Univ Sci & Technol China, Sch Life Sci, Dept Chem, Hefei Natl Lab Phys Sci Microscale, Hefei 230009, Anhui, Peoples R China 6.Hefei Univ Technol, Sch Food & Biol Engn, Hefei 230009, Anhui, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Rui,Shi, Pan,Chen, Junyou,et al. Chemical synthesis and biological activity of peptides incorporating an ether bridge as a surrogate for a disulfide bond[J]. CHEMICAL SCIENCE,2020,11.
APA	Zhao, Rui.,Shi, Pan.,Chen, Junyou.,Sun, Shuaishuai.,Chen, Jingnan.,...&Li, Yi-Ming.(2020).Chemical synthesis and biological activity of peptides incorporating an ether bridge as a surrogate for a disulfide bond.CHEMICAL SCIENCE,11.
MLA	Zhao, Rui,et al."Chemical synthesis and biological activity of peptides incorporating an ether bridge as a surrogate for a disulfide bond".CHEMICAL SCIENCE 11(2020).