IR@PKUHSC  > 北京大学药学院  > 化学生物学系
学科主题药学
An effective approach to artificial nucleases using copper(II) complexes bearing nucleobases
Wang, Jin-Tao1; Xia, Qing2; Zheng, Xiao-Hui1; Chen, Huo-Yan1; Chao, Hui1; Mao, Zong-Wan1,2; Ji, Liang-Nian1
刊名DALTON TRANSACTIONS
2010
DOI10.1039/b915392f
39期:8页:2128-2136
收录类别SCI
文章类型Review
WOS标题词Science & Technology
类目[WOS]Chemistry, Inorganic & Nuclear
资助者National Natural Science Foundation of China ; Guangdong Provincial Natural Science Foundation ; 973 Program ; National Natural Science Foundation of China ; Guangdong Provincial Natural Science Foundation ; 973 Program
研究领域[WOS]Chemistry
关键词[WOS]DOUBLE-STRAND DNA ; ZINC-COMPLEXES ; HYDROLYTIC CLEAVAGE ; MITSUNOBU REACTION ; METAL-COMPLEXES ; MINOR-GROOVE ; DISUBSTITUTED 2,2&prime ; -BIPYRIDINE ; PHOSPHODIESTER HYDROLYSIS ; CARBOCYCLIC NUCLEOSIDES ; BIOLOGICAL EVALUATION
英文摘要

Novel copper(II) complexes bearing 2,2′-bipyridine (bpy) derivatives with adenine, thymine and uracil nucleobases [Cu(L(1))Cl(2)]center dot 2H(2)O (1), [Cu(L(2))Cl(2)] (2) and [Cu(L(3))Cl(2)]center dot H(2)O (3) (L(1) = 5,5′-Di[N9-adenylmethyl]-2,2′-bipyridine, L(2) = 5,5′-Di[N1-thyminylmethyl]-2,2′-bipyridine and L(3) = 5,5′-Di[N1-uracilmethyl]-2,2′-bipyridine) were synthesized and characterized. Structure simulation was performed for these complexes. Circular dichroism (CD) spectra revealed the interactions between these ligands and pBR322 DNA and showed that the local DNA structure was perturbed by these ligands. Cleavage of pBR322 DNA by these complexes was carried out in 20 mM HEPES (pH 7.5) at 37 degrees C. The calculated pseudo-Michaelis-Menten kinetic parameters (k(cat)) were 14.7 +/- 0.6 and 40.4 +/- 1.3 h(-1) for 1 and 2. The cleavage efficiency of 2 was 80-fold higher than that of its simple analogue [Cu(bpy)Cl(2)] (k(cat) = 0.50 h(-1)) and very close to the catalytic rate constant of natural EcoRI endonuclease (k(cat) = 43.2 h(-1)) at similar conditions. Thus, complex 2 might be one of the most effective artificial nucleases that could catalyze double-stranded DNA hydrolytic cleavage so far. Hydrolytic mechanisms involved in DNA cleavage were explored using radical scavengers and T4 ligase. Competitive experiments with special binding agents showed that complexes 1-3 could preferentially bind to the minor groove of double-stranded DNA, suggesting specific DNA binding characteristics. Molecular docking calculations also indicated that complexes 1-3 could bind to the minor groove of targeted DNA much more strongly than their simple analogues and preferentially bind at the AT region of the dodecamer. Such high DNA cleavage ability and selectivity of these copper(II) complexes could be attributed to the synergic effects of the metal center and the pendant nucleobases.

语种英语
所属项目编号20821001 ; 20831006 ; 20725103 ; 30770494 ; 9351027501000003 ; 2007C B815306
资助者National Natural Science Foundation of China ; Guangdong Provincial Natural Science Foundation ; 973 Program ; National Natural Science Foundation of China ; Guangdong Provincial Natural Science Foundation ; 973 Program
WOS记录号WOS:000274405200033
Citation statistics
Cited Times:44[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66163
Collection北京大学药学院_化学生物学系
作者单位1.Sun Yat Sen Univ, Sch Chem & Chem Engn, MOE Key Lab Bioinorgan & Synth Chem, Guangzhou 510275, Guangdong, Peoples R China
2.Peking Univ, Dept Biol Chem, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drug, Beijing 100191, Peoples R China
Recommended Citation
GB/T 7714
Wang, Jin-Tao,Xia, Qing,Zheng, Xiao-Hui,et al. An effective approach to artificial nucleases using copper(II) complexes bearing nucleobases[J]. DALTON TRANSACTIONS,2010,39(8):2128-2136.
APA Wang, Jin-Tao.,Xia, Qing.,Zheng, Xiao-Hui.,Chen, Huo-Yan.,Chao, Hui.,...&Ji, Liang-Nian.(2010).An effective approach to artificial nucleases using copper(II) complexes bearing nucleobases.DALTON TRANSACTIONS,39(8),2128-2136.
MLA Wang, Jin-Tao,et al."An effective approach to artificial nucleases using copper(II) complexes bearing nucleobases".DALTON TRANSACTIONS 39.8(2010):2128-2136.
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