Pollack Michael, Oe Tomoyuki, Lee Seon Hwa, Silva Elipe Maria Victoria, Arison Byron H, Blair Ian A
Center for Cancer Pharmacology, University of Pennsylvania School of Medicine, 1254 BRB II/III, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104-6160, UK.
Chem Res Toxicol. 2003 Jul;16(7):893-900. doi: 10.1021/tx030009p.
Analysis of the reaction between 2'-deoxycytidine and 4-oxo-2-nonenal by LC/MS revealed the presence of three major products (adducts A(1), A(2), and B; M + H = 364). Adducts A(1) and A(2) were isomeric, and each dehydrated to form adduct B. The structure of adduct B was shown by LC/MS and NMR spectroscopy to be an etheno-2'-deoxycytidine adduct 1' '-[1-(2'-deoxy-beta-d-erythro-pentofuranosyl)-1H-imidazo[2,1-c]pyrimidin-2-oxo-4-yl]heptane-2' '-one. A time course experiment performed at 65 degrees C (pH 5-8) showed that the transformation of both A(1) and A(2) was pH-dependent. In acidic conditions, adducts A(1) and A(2) dehydrated primarily to adduct B. In contrast, in basic conditions, adducts A(1) and A(2) hydrolyzed primarily to dCyd. The data are consistent with adducts A(1) and A(2) being substituted ethano adducts that dehydrate to adduct B, a substituted 3,N(4)-etheno-2'-deoxycytidine adduct.
通过液相色谱/质谱联用（LC/MS）分析2'-脱氧胞苷与4-氧代-2-壬烯醛之间的反应，结果显示存在三种主要产物（加合物A(1)、A(2)和B；M + H = 364）。加合物A(1)和A(2)是同分异构体，且各自脱水形成加合物B。通过LC/MS和核磁共振光谱（NMR）确定加合物B的结构为1''-[1-(2'-脱氧-β-D-赤藓戊呋喃糖基)-1H-咪唑并[2,1-c]嘧啶-2-氧代-4-基]庚烷-2''-酮。在65℃（pH 5 - 8）下进行的时间进程实验表明，A(1)和A(2)的转化均依赖于pH值。在酸性条件下，加合物A(1)和A(2)主要脱水形成加合物B。相反，在碱性条件下，加合物A(1)和A(2)主要水解为脱氧胞苷（dCyd）。这些数据与加合物A(1)和A(2)是脱水形成加合物B（一种取代的3,N(4)-乙烯基-2'-脱氧胞苷加合物）的取代乙烷加合物的结论一致。
