Towards artificial repair of UV-damaged DNA: studies on drug binding and alkali hydrolysis.

Shigenori Iwai, Aki Inase, Sharif Jafar, Miho Higurashi, Takashi Ohtsuki, Yan Xu, Hiroshi Sugiyama
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Abstract

Properties of the DNA containing the (6-4) photoproduct, one of the major UV-induced lesions, were analyzed. Two basic studies towards artificial recognition and repair of this type of damaged DNA are presented here. One is recognition of the UV-damaged DNA by a minor groove-binding drug. It was found by CD spectroscopy that distamycin could bind DNA duplexes containing the (6-4) photoproduct as effectively as the unmodified DNA, whereas a DNA duplex containing the cyclobutane pyrimidine dimer was not recognized by this drug. The other is a mechanistic study on alkali degradation of this photoproduct. HPLC and NMR analyses revealed that hydrolysis between the N3 and C4 positions of the 5' pyrimidine component occurred first. This intermediate was relatively stable, and further degradation to the strand break required severe conditions like the hot piperidine treatment.

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紫外线损伤DNA的人工修复:药物结合和碱水解的研究。
分析了含有(6-4)光产物的DNA的性质,这是紫外线诱导的主要病变之一。本文介绍了人工识别和修复这类受损DNA的两项基本研究。一种是通过一种微小的凹槽结合药物来识别紫外线损伤的DNA。CD光谱分析发现,二霉素能与未修饰的DNA一样有效地结合含有(6-4)光产物的DNA双链,而含有环丁烷嘧啶二聚体的DNA双链则不能被该药识别。二是该光产物碱降解机理的研究。HPLC和NMR分析表明,5′嘧啶组分的N3和C4位点之间首先发生水解。该中间体相对稳定,进一步降解到链断裂需要像热哌啶处理这样的苛刻条件。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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