氨基噻唑酮Cu(Ⅱ)核酸酶的合成、结构及活性研究  

Nuclease of amino-thiazolidinone Cu(Ⅱ): synthesis, structure and activity

作　　者：邵佳[1] 徐靖源[2] 

机构地区：[1]天津市第一中心医院药学部,天津300192 [2]天津医科大学药学院,天津市临床药物关键技术重点实验室,天津300070

出　　处：《天津医科大学学报》2016年第6期474-477,共4页Journal of Tianjin Medical University

基　　金：国家自然科学基金资助项目(21371135)

摘　　要：目的:探究氨基噻唑酮Cu(Ⅱ)核酸酶的合成、晶体结构及其活性,预期得到一种高效的体外化学核酸酶试剂。方法:利用单晶衍射、琼脂糖凝胶电泳分别确定氨基噻唑酮Cu(Ⅱ)核酸酶试剂的空间结构及其活性。结果:氨基噻唑酮Cu(Ⅱ)核酸酶试剂为单斜晶系,空间群为P2(1)/n,由单个[Cu(TZD)Br_2](1)(TZD=(Z)-3-methyl-2-((E)-(1-phenylethylidene)hydrazono)-thiazolidin-4-one)单元组成,相比原来配合物[Cu(4ML)Cl],经改造后的1在外界诱导剂的存在下30μmol/L即可将DNA由Form Ⅰ完全转变为Form Ⅱ,核酸酶活性提高10倍以上,核酸酶机制以氧化切割为主。结论:该研究获得一种氨基噻唑酮配体和一个新颖的氨基噻唑酮Cu(Ⅱ)配合物,并表征其晶体结构,1作为一种高效的核酸酶试剂,其能力比[Cu(4ML)Cl]提高一个数量级,可作为一种潜在的抗肿瘤药物。Objective To study the synthesis, crystal structure and nuclease activity of the amino-thiazolidinone Cu （Ⅱ） nuclease reagent,and to obtain an efficient chemical nuclease reagent in vitro. Methods： The crystal structure and nuclease actieity of Cu （Ⅱ） nucleasereagent were discussed by X-ray and agarose gel electrophoresis. Results： The Cu（Ⅱ） complex was monoelinic, space group P2（1）/n, and itconsisted of a [Cu （TZD）Br2] （1） （TZD = （Z）-3-methyl-2-（（E）-（1-phenylethylidene）hydrazono） -thiazolidin-4-one） unit; the nucleaseactivity of 1（30 txmol/L） could make most of Form I transform into Form II with inducer, and it was increased over 10-fold compared with [Cu（4ML）C1]; its nuelease mechanism was oxidative cleavage. Conclusion： An amino-thiazolidinone ligand and a novel amino-thiazolidinoneCu（II） nuclease reagent could be acquired. Cu（TZD）Br2 capability is on a higher magnitude compared with [Cu（4ML）C1], which can be usedas a potential anti-tumor drug.

关 键 词：氨基噻唑酮 Cu(Ⅱ)配合物 晶体结构 核酸酶 

分 类 号：R9[医药卫生—药学]