苯醌-脱氧鸟苷酸加合物的结构及化学特性初步研究

Preliminary study on structure and chemical characteristics of deoxyguanoside-benzoquinone adducts

目的 测定苯醌 (BQ)与脱氧鸟苷酸 (dGMP)反应形成的加合物结构与化学特性。方法高效液相色谱 质谱联机技术及紫外分光光度法。结果 苯醌与脱氧鸟苷酸反应形成两种可检测的加合物Ad1 和Ad2 ,质谱显示Ad1 的分子量为 437,在不同pH条件下的特征紫外吸收光谱及结合键类型测定结果表明 ,Ad1 为BQ与dGMP共价结合而成 ,推测结合位点在dGMP的N 1和N2 位 ,分子式为C1 6 H1 6 O8N5P。BQ与小牛胸腺DNA反应水解产物经高效液相色谱 (HPLC)分离同样检出了与Ad1 具有相同保留时间的化合物。Ad2 分子量为 2 4 1 ,其分子式为C1 1 H7O2 N5,可能是由BQ进攻dGMP的N 9位并脱掉糖基所得。结论 苯醌可在体外试管反应条件下形成DNA加合物 ,其中一种主要的加合物结构为 (3’ 羟基 ) 1 ,N2 苯乙烯基 2’ 脱氧鸟苷 5’

Objective To detect the structure and chemical characteristics of the adduct from the reaction of p benzoquinone(BQ) with deoxyguanoside(dGMP). Methods dGMP and calf thymus DNA were reacted with BQ in buffered solutions with neutral pH,the reaction products were separated and purified by high performance liquid chromatograph(HPLC),and then characterized by UV spectroscopy and mass spectrometry. Results The reaction of BQ with dGMP yielded two adduct products(Ad 1 and Ad 2 respectively).The characterized results of Ad 1 suggested that BQ reacted at the N 1 and N 2 position of dGMP by losing one H 2O molecule,the molecular weight of Ad 1 was 437,and the molecular formula was C 16 H 16 O 8N 5P.Ad 1 could also be detected from calf thymus DNA reacted with BQ in vitro,which possessed the same elution profile by HPLC analysis.Meanwhile,Ad 2 was detected in the experimental condition.It was proposed that Ad 2 was formed by BQ reacted at the N 9 position of dGMP by losing one molecule of deoxyribose,the molecular weight was 241,and the molecular formula was C 11 H 7O 2N 5. ConclusionThe structure of one major adduct from reaction of BQ with DNA is (3' OH) 1,N 2 C 6H 5CH 2' deoxyguanosine 5' monophosphate.