Studies on Cleavage of Modified DNA

为了研究修饰后的DNA的反应性，合成了C4‘位脱氧核糖氧化得到的碱不稳定损伤(1)，并对C4’修饰的核苷酸衍生物进行了反应性研究。1)合成了C4’硒化核苷酸衍生物(2)作为不稳定物1的前体，2与NBS反应得到1，表明2可以作为1.2的合适前体。合成了可能参与碱催化碱不稳定物(1)分解的核苷衍生物(3)。胺处理1产生一个核苷酸片段具有3'-磷酸末端和内酰胺。特别是在中性和酸性条件下，1的胺处理可以获得高产的内酰胺和核苷酸片段。提出了1生成核苷酸片段和内酰胺的反应机理，深入了解了胺诱导的碱不稳定病变的降解机理。3) NBS处理C4‘硒化核苷酸衍生物(4)得到C4’氧化核苷酸衍生物(5)，模型简单为1。5与胺在pH8下反应得到内酰胺，产率为40%。结果表明，1可能在生理条件下通过5元胺中间体与胺反应生成内酰胺和核苷酸片段。

In order to investigate the reactivity of modified DNA,the alkali labile lesion (1), which is obtained by oxidation of deoxyribose at the C4' position, C4' modified nucleotide derivatives were synthesized and their reactivities were studied.1) C4' Selenated nucleotide derivative (2) was synthesized as a precursor of unstable 1 and the reaction of 2 with NBS gave 1 to show that 2 can be used as a proper precursor of 1.2) The nucleoside derivative (3), which might be involved in the base-catalyzed decomposition of the alkali labile lesion(1), was synthesized. Amine treatment of 1 produced a nucleotide fragment having 3'-phosphate termini and lactam. Especially under neutral and acidic conditions, amine treatment of 1 afforded lactam in good yield as well as nucleotide fragment. The reaction mechanism of the formation of nucleotide fragment and lactam from 1 was proposed, giving insight into the mechanism of the amine-induced degradation of the alkali labile lesion.3) NBS treatment of C4' selenated nucleotide derivative (4) afforded the C4' oxidized nucleotide derivative (5), a simple model of 1. The reaction of 5 with amine at pH8 gave lactam in 40% yield. This result showed that 1 might react with amine under physiological conditions to give lactam and nucleotide fragment via 5 membered amine intermediate.