DNA binding and cleaving activity of the new cleft molecule N,N'-Bis(guanidinoethyl)-2,6-pyridinedicarboxamide in the absence or in the presence of copper(II).
DNA binding and cleaving activity of the new cleft molecule N,N'-Bis(guanidinoethyl)-2,6-pyridinedicarboxamide in the absence or in the presence of copper(II).
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DOI:
10.1021/bc800062g
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发表时间:
2008-08
影响因子:
4.7
通讯作者:
Y. Shao;Xin Sheng;Ying Li;Zhao-Li Jia;Jingjing Zhang;Fang Liu;Guoyuan Lu
中科院分区:
文献类型:
--
作者:
Y. Shao;Xin Sheng;Ying Li;Zhao-Li Jia;Jingjing Zhang;Fang Liu;Guoyuan Lu
Novel cleft molecule pyridine-2,6-dicarboxamide appending two guanidinoethyl group side arms (Gua) was synthesized. The interactions of the cleft molecule in the absence of copper(II) (Gua) or in the presence of copper(II) (Cu2+-Gua) with calf thymus DNA were studied by fluorescence and CD spectroscopy. The results indicate that the DNA binding affinity of Cu2+-Gua is stronger than that of Gua, and the binding constants of Cu2+-Gua and Gua are 1.61 x 10(6) M(-1) and 2.86 x 10(5) M(-1), respectively. Agarose gel electrophoresis was used to assess the plasmid pUC 19 DNA cleavage activities in the presence of Gua and Cu2+-Gua. Kinetic data of DNA cleavage promoted by Cu2+-Gua under physiological conditions fit a saturation kinetic profile with k(max) of 0.0173 +/- 0.0011 h(-1), which gave a aproximately 10(6)-fold rate acceleration over uncatalyzed supercoiled DNA, while the catalyst concentration is lower than 0.0625 mM. The hydrolysis pathway was proposed as the possible mechanism for DNA cleavage promoted by Cu2+-Gua. The acceleration is due to efficient cooperative catalysis of the copper cation center and the functional groups (bis(guanidinium) groups).