Choi Sunhee, Cooley Richard B, Hakemian Amanda S, Larrabee Yuna C, Bunt Richard C, Maupas Stéphane D, Muller James G, Burrows Cynthia J
Department of Chemistry and Biochemistry, Middlebury College, Middlebury, Vermont 05753, USA.
J Am Chem Soc. 2004 Jan 21;126(2):591-8. doi: 10.1021/ja038334m.
Many transition metal complexes mediate DNA oxidation in the presence of oxidizing radiation, photosensitizers, or oxidants. The final DNA oxidation products vary depending on the nature of metal complexes and the structure of DNA. Here we propose a mechanism of oxidation of a nucleotide, deoxyguanosine 5'-monophosphate (dGMP) by trans-d,l-1,2-diaminocyclohexanetetrachloroplatinum (trans-Pt(d,l)(1,2-(NH(2))(2)C(6)H(10))Cl(4), [Pt(IV)Cl(4)(dach)]; dach = diaminocyclohexane) to produce 7,8-dihydro-8-oxo-2'-deoxyguanosine 5'-monophosphate (8-oxo-dGMP) stoichiometrically. The reaction was studied by high-performance liquid chromatography (HPLC), (1)H and (31)P nuclear magnetic resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). The proposed mechanism involves Pt(IV) binding to N7 of dGMP followed by cyclization via nucleophilic attack of a phosphate oxygen at C8 of dGMP. The next step is an inner-sphere, two-electron transfer to produce a cyclic phosphodiester intermediate, 8-hydroxyguanosine cyclic 5',8-(hydrogen phosphate). This intermediate slowly converts to 8-oxo-dGMP by reacting with solvent H(2)O.
许多过渡金属配合物在存在氧化辐射、光敏剂或氧化剂的情况下介导DNA氧化。最终的DNA氧化产物因金属配合物的性质和DNA的结构而异。在此，我们提出了一种由反式-d，l-1，2-二氨基环己烷四氯铂（反式-Pt（d，l）（1，2-（NH₂）₂C₆H₁₀）Cl₄，[Pt（IV）Cl₄（dach）]；dach = 二氨基环己烷）氧化核苷酸5'-单磷酸脱氧鸟苷（dGMP）以化学计量方式产生7，8-二氢-8-氧代-2'-脱氧鸟苷5'-单磷酸（8-氧代-dGMP）的机制。通过高效液相色谱（HPLC）、¹H和³¹P核磁共振（NMR）以及电喷雾电离质谱（ESI-MS）对该反应进行了研究。所提出的机制包括Pt（IV）与dGMP的N7结合，随后通过dGMP的C8处的磷酸氧的亲核攻击进行环化。下一步是内球双电子转移以产生环状磷酸二酯中间体，8-羟基鸟苷环状5'，8-（磷酸氢）。该中间体通过与溶剂H₂O反应缓慢转化为8-氧代-dGMP。
