Bergeron François, Klarskov Klaus, Hunting Darel J, Wagner J Richard
Group in the Radiation Sciences, Department of Pharmacology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec J1H 4N5, Canada.
Chem Res Toxicol. 2007 May;20(5):745-56. doi: 10.1021/tx6002968. Epub 2007 Mar 31.
Near-UV photolysis of 2-methyl-1,4-naphthoquinone (MQ, menadione) tethered DNA induces initial charge transfer followed by either transport of the damage to G or the formation of interstrand cross-links between MQ and DNA bases. In this work, the products responsible for interstrand cross-links have been characterized by mass spectrometry, NMR, and comparison with model compounds. Three major products were formed in the photolysis of MQ-DNA duplexes. Two of the products (isomers) have a cross-link between C2 of a 2,3-saturated MQ moiety and N6 of a dAdo moiety. These products readily convert back to MQ and dAdo upon heating in neutral solution, and thus, they lead to reversible cross-links in MQ-DNA duplexes. The third product has a cross-link between C3 of a 2,3-unsaturated MQ moiety and N6 of an dAdo moiety. This product was stable in neutral solution. The formation of MQ to A cross-links in DNA may be explained by the coupling of MQ radicals that arise from the protonation of MQ radical anions, together with adenin-N6-yl radicals that arise from the deprotonation of A radical cations.
与2-甲基-1,4-萘醌（MQ，甲萘醌）相连的DNA在近紫外光解作用下会引发初始电荷转移，随后损伤要么转移至鸟嘌呤（G），要么在MQ与DNA碱基之间形成链间交联。在这项工作中，通过质谱、核磁共振（NMR）以及与模型化合物对比，对导致链间交联的产物进行了表征。MQ-DNA双链体光解过程中形成了三种主要产物。其中两种产物（异构体）在2,3-饱和MQ部分的C2与脱氧腺苷（dAdo）部分的N6之间存在交联。这些产物在中性溶液中加热时很容易变回MQ和dAdo，因此，它们会导致MQ-DNA双链体中出现可逆交联。第三种产物在2,3-不饱和MQ部分的C3与dAdo部分的N6之间存在交联。该产物在中性溶液中稳定。DNA中MQ与腺嘌呤（A）之间交联的形成可以通过MQ自由基阴离子质子化产生的MQ自由基与A自由基阳离子去质子化产生的腺嘌呤-N6-基自由基的偶联来解释。
