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采用大环多胺配体构筑金属模拟水解酶活性中心还是一个十分有待深入研究和发展的切割系统。本项目基于水解型切割DNA中的磷酸二酯键,设计合成带有有机胍基、氨基、羟基等基团侧链基... 采用大环多胺配体构筑金属模拟水解酶活性中心还是一个十分有待深入研究和发展的切割系统。本项目基于水解型切割DNA中的磷酸二酯键,设计合成带有有机胍基、氨基、羟基等基团侧链基团的单环和多环大环三胺和大环四胺,进而合成多种金属离子的单核和多核大环配合物;用所合成的模型配合物对磷酸二酯键模型化合物BDNPP和BNPP等进行水解活性的测定,给出水解动力学参数;用所合成的模型配合物对寡聚核苷酸、DNA进行识别、切割研究;利用电喷雾质谱研究配合物在溶液中的结构,为揭示切割机理研究提供配位化合物的结构信息;预期能获得若干种具有良好识别和切割功能的新的DNA切割试剂,并有助于对能特异性识别DNA的配合物和水解型切割剂的性质、特点以及机理有较深入的认识,为进一步发展具有DNA切割功能的配合物和基因治疗药物提供借鉴,在核酸切割剂的理论和应用方面取得一些有价值的进展。
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luona919
2013-03-06
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The macrocyclic polyamine ligands metal mimic hydrolase activity center is a very in-depth study and development of the cutting system. The hydrolysis cleavage in DNA two phosphate ester based on the design, synthesis of monocyclic and polycyclic ring with organic guanidine, amino, hydroxyl group side chain groups of three amines and large ring four amine, mononuclear and multinuclear macrocyclic complexes and synthesis of various metal ions; Determination of complex hydrolysis activity the two phosphate bond model compounds BDNPP and BNPP with the synthetic model, gives the hydrolysis kinetics parameters; with the use of synthetic model complexes of oligonucleotides, DNA identification, cutting research using electrospray ionization mass spectrometry; structure of complexes in solution, provide structural information of coordination compounds as to reveal the cutting mechanism research; expected to obtain some kind of good recognition and cutting function of the new DNA cleavage reagent, and contribute to the complex and hydrolysis of can specifically recognize the DNA cutting properties, characteristics and mechanism of agent has a more in-depth understanding, has provided reference complexes and gene therapy drug DNA cutting function for further development, made some valuable progress in cutting theory and application agent in nucleic acid.
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