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首页> 外文期刊>Biochemistry >Interaction of a spin-labeled adenine-acridine conjugate with a DNA duplex containing an abasic site model.
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Interaction of a spin-labeled adenine-acridine conjugate with a DNA duplex containing an abasic site model.

机译：旋转标记的腺嘌呤-ac啶共轭物与含有无碱基位点模型的DNA双链体的相互作用。

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摘要

The abasic site is a common lesion in DNA that is also formed as an intermediate in the base excision repair of damaged bases. We have previously reported the adenine-acridine conjugate 1 that was designed to bind to the abasic site and interfere with the repair process. High-field NMR had shown that 1 forms specific complexes with a DNA duplex containing an apurinic abasic site model. We report here the dynamics of the interaction of the nitroxide-labeled analogue 3 of the conjugate 1 with the same apurinic oligonucleotide and with the parent unmodified duplex. Identical study of the labeled acridine subunit 5 used as a reference is also reported. In the presence of the apurinic duplex and depending on the concentrations and drug ratios, three species are observed: the radical "free in solution", the "intercalation" complex characterized by its similarity to that observed in the presence of the parent unmodified duplex, and the "abasic-site-specific" complex which is the sole species visible at low drug ratios. The experimental data reinforced by molecular modeling of the complex and theoretical calculation of correlation times suggest (i) the most immobilized form corresponds to that observed by NMR and (ii) complexation of the drug is little or not modified by the spin-label. We also show that the abasic site constitutes a binding site for the propylaminoacridine intercalator 5.
机译：无碱基位点是DNA中的常见病变，其也形成为受损碱基的碱基切除修复中的中间体。我们以前曾报道过腺嘌呤-ac啶共轭物1旨在结合到无碱基位点并干扰修复过程。高场NMR显示1与含有嘌呤无碱基位点模型的DNA双链体形成特定的复合物。我们在这里报告了共轭物1的氮氧化物标记类似物3与相同的嘌呤寡核苷酸和未修饰的亲本双链体相互作用的动力学。还报道了用作参考的标记a啶亚基5的相同研究。在存在嘌呤双链体时，根据浓度和药物比例，观察到三种：自由基“溶液中游离”，“嵌入”复合物，其特征在于与母体未修饰双链体存在的相似性，以及“绝对位置特异性”复合物，这是在低药物比率下可见的唯一物种。通过复杂分子模型建模和相关时间的理论计算得到的实验数据表明，（i）固定化程度最高的形式对应于NMR观察到的形式;（ii）药物的复合作用很少或没有被旋转标记修饰。我们还表明，无碱基位点构成了丙基氨基ac啶嵌入剂5的结合位点。

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