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新型四肽配合物 Cu(II)/Zn(II)-Ala-Pro-Ala-Pro 的合成、DNA 识别与切割研究。

Synthesis, DNA recognition and cleavage studies of novel tetrapeptide complexes, Cu(II)/Zn(II)-Ala-Pro-Ala-Pro.

机构信息

Department of Chemistry, Aligarh Muslim University, Aligarh 202 002, Uttar Pradesh, India.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2013 May;108:151-8. doi: 10.1016/j.saa.2013.01.059. Epub 2013 Feb 1.

Abstract

New tetrapeptide complexes Cu(II)·Ala-Pro-Ala-Pro (1) and Zn(II)·Ala-Pro-Ala-Pro (2) were synthesized from the reaction of tetrapeptide, Ala-Pro-Ala-Pro and CuCl2/ZnCl2 and were thoroughly characterized by elemental analysis, IR,(1)H and (13)C NMR (in case of 2), ESI-MS, UV and molar conductance measurements. The solution stability study was carried out employing UV-vis absorption titrations over a broad range of pH which suggested the stability of the complexes in solution. In vitro interaction of complexes 1 and 2 with CT-DNA was studied employing UV-vis, fluorescence, circular dichroic and viscometry studies. To throw insight into molecular binding event at the target site, UV-vis titrations of 1 and 2 with mononucleotides of interest viz.; 5'-GMP and 5'-TMP were carried out. Cleavage activity of the complexes with pBR322 plasmid DNA was evaluated by agarose gel electrophoresis and, the electrophoresis pattern demonstrated that both the complexes 1 and 2 are efficient cleavage agents. Further, the Cu(II) complex displayed efficient oxidative cleavage of supercoiled DNA while various reactive oxygen species are responsible for the cleavage in Zn(II) complex.

摘要

新的四肽配合物 Cu(II)·Ala-Pro-Ala-Pro (1) 和 Zn(II)·Ala-Pro-Ala-Pro (2) 是由四肽 Ala-Pro-Ala-Pro 与 CuCl2/ZnCl2 反应合成的,并通过元素分析、IR、(1)H 和 (13)C NMR(对于 2)、ESI-MS、UV 和摩尔电导率测量进行了彻底的表征。通过在宽 pH 范围内进行 UV-vis 吸收滴定进行溶液稳定性研究,表明配合物在溶液中的稳定性。采用 UV-vis、荧光、圆二色性和粘度研究研究了配合物 1 和 2 与 CT-DNA 的体外相互作用。为了深入了解靶位点的分子结合事件,进行了与感兴趣的单核苷酸(即 5'-GMP 和 5'-TMP)的 1 和 2 的 UV-vis 滴定。通过琼脂糖凝胶电泳评估了配合物与 pBR322 质粒 DNA 的切割活性,电泳图谱表明两种配合物 1 和 2 都是有效的切割剂。此外,Cu(II) 配合物显示出有效氧化切割超螺旋 DNA,而各种活性氧物种负责 Zn(II) 配合物的切割。

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