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铜(II)-阿米卡星复合物对DNA和RNA的损伤

DNA and RNA damage by Cu(II)-amikacin complex.

作者信息

Jezowska-Bojczuk Małgorzata, Szczepanik Wojciech, Leśniak Wojciech, Ciesiołka Jerzy, Wrzesiński Jan, Bal Wojciech

机构信息

Faculty of Chemistry, University of Wrocław, Wrocław, Poland; Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland.

出版信息

Eur J Biochem. 2002 Nov;269(22):5547-56. doi: 10.1046/j.1432-1033.2002.03260.x.

DOI:10.1046/j.1432-1033.2002.03260.x
PMID:12423353
Abstract

The oxidation-promoting reactivity of copper(II) complex of aminoglycosidic antibiotic amikacin [Cu(II)-Ami] in the presence of hydrogen peroxide, was studied at pH 7.4, using 2'-deoxyguanosine (dG), pBR322 plasmid DNA and yeast tRNAPhe as target molecules. The mixtures of complex with H2O2 were found to be efficient oxidants, converting dG to its 8-oxo derivative, generating strand breaks in plasmid DNA and multiple cleavages in tRNAPhe. The complex underwent autooxidation as well, with amikacin hydroperoxides as likely major products. This reactivity pattern was found to be due to a combination of metal-bound and free hydroxyl radicals.

摘要

在pH 7.4条件下,以2'-脱氧鸟苷(dG)、pBR322质粒DNA和酵母苯丙氨酸转运RNA(tRNAPhe)为靶分子,研究了氨基糖苷类抗生素阿米卡星的铜(II)配合物[Cu(II)-Ami]在过氧化氢存在下的氧化促进反应活性。发现该配合物与过氧化氢的混合物是有效的氧化剂,可将dG转化为其8-氧代衍生物,在质粒DNA中产生链断裂,并在tRNAPhe中产生多处切割。该配合物也会发生自氧化,可能以阿米卡星氢过氧化物作为主要产物。发现这种反应模式是由金属结合的羟基自由基和游离羟基自由基共同作用导致的。

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