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关于诺加霉素、阿柔比星、去甲柔红霉素和维里普兰宁与DNA相互作用的足迹分析研究。

Footprinting studies on the interactions of nogalamycin, arugomycin, decilorubicin and viriplanin with DNA.

作者信息

Fox K R

机构信息

Department of Physiology and Pharmacology, University of Southampton, UK.

出版信息

Anticancer Drug Des. 1988 Dec;3(3):157-68.

PMID:3207463
Abstract

DNase I footprinting studies employing several DNA fragments have confirmed that nogalamycin binds preferentially to regions of DNA containing alternating purines and pyrimidines. Arugomycin and viriplanin A, related compounds which contain additional sugar residues at both ends of the molecule, produce similar patterns of nuclease protection though at higher drug concentrations. The pattern induced by decilorubicin, which has charged groups at both ends of the aglycone, differs in many details and this analogue appears to display a modified DNA sequence selectivity. The results have been confirmed by similar studies using DNase II. All four compounds increase the susceptibility of certain adenine residues to modification by diethylpyrocarbonate. The results suggest an intercalative mode of binding for these nogalamycin analogues, and reveals an increased complexity in compounds which can bind to DNA by this mechanism.

摘要

使用多个DNA片段进行的脱氧核糖核酸酶I足迹研究证实,诺加霉素优先结合到含有交替嘌呤和嘧啶的DNA区域。阿柔比星和viripaninin A是相关化合物,在分子两端含有额外的糖残基,尽管药物浓度较高,但也会产生类似的核酸酶保护模式。柔红霉素在糖苷配基两端带有电荷基团,其诱导的模式在许多细节上有所不同,这种类似物似乎表现出改变的DNA序列选择性。使用脱氧核糖核酸酶II的类似研究证实了这些结果。所有这四种化合物都增加了某些腺嘌呤残基被焦碳酸二乙酯修饰的敏感性。结果表明这些诺加霉素类似物的结合模式为嵌入模式,并揭示了通过这种机制与DNA结合的化合物的复杂性增加。

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