Chloride ions catalyze the formation of cis adducts in the binding of anti-benzo[a]pyrene diol epoxide to nucleic acids.
Chloride ions catalyze the formation of cis adducts in the binding of anti-benzo[a]pyrene diol epoxide to nucleic acids.
复制标题
氯离子在抗苯并[a]芘二醇环氧化物与核酸的结合中催化顺式加合物的形成。
DOI：
10.1073/pnas.91.4.1371
复制
发表时间：
1994
影响因子：
11.1
通讯作者：
Meehan,T
中科院分区：
文献类型：
--
作者：
Wolfe,AR;Yamamoto,J;Meehan,T
外消旋 7r,8t-二羟基-9t,10t-环氧-7,8,9,10-四氢苯并[a]芘（抗 BPDE）对 DNA 的烷基化表现出强烈偏好在 N2 脱氧鸟苷烷基化位点和抗 BPDE 的 (+)-对映体之间形成反式加合物。在不添加盐的 10 mM 缓冲液存在下，与天然小牛胸腺 DNA 形成的加合物中 98% 是由环氧化物环的反式打开产生的。在低盐浓度下，使用双链 DNA 获得的反式加合物形成的强选择性在 Poly(G) 中表现得较小，但在 dAMP 中几乎不存在。当 DNA 加合物在 10 mM MgCl2 或 1 M NaCl 中形成时，顺式加合物的比例分别增加至约 7% 和约 26%。在低盐、10 mM MgCl2 和 1 M NaCl 下，脱氧鸟苷加合物的顺式分别约为 1%、6% 和 24%，而脱氧腺苷加合物的顺式分别约为 11%、14% 和 37%。 NaCl 还增加与聚 (G) 和 dAMP 形成的顺式加合物的比例。据推测，由于盐导致顺式加合物形成的增加是由于氯离子对 BPDE 碳阳离子的 SN1 攻击，形成反式氯醇，然后是 DNA 的 SN2 攻击。
The alkylation of DNA by racemic 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) exhibits a strong preference for formation of trans adducts between the N2 deoxyguanosine alkylation site and the (+)-enantiomer of anti-BPDE. In the presence of 10 mM buffer with no added salt, 98% of the adducts formed with native calf thymus DNA result from trans opening of the epoxide ring. The strong selectivity for trans adduct formation obtained with duplex DNA at low salt concentration is found to a lesser degree with poly(G) but is nearly absent with dAMP. When DNA adducts are formed in 10 mM MgCl2 or 1 M NaCl, the proportion of cis adducts increases to approximately 7 and approximately 26%, respectively. At low salt, 10 mM MgCl2, and 1 M NaCl, deoxyguanosine adducts are approximately 1%, 6%, and 24% cis, whereas deoxyadenosine adducts are approximately 11%, 14%, and 37% cis, respectively. NaCl also increases the proportion of cis adducts formed with poly(G) and dAMP. It is proposed that the increase in cis-adduct formation due to salt results from SN1 attack of chloride ion on the BPDE carbocation, forming a trans chlorohydrin, followed by SN2 attack of DNA.
外来化合物的生物活化
DOI：
--
发表时间：
1985
期刊：
影响因子：
--
作者：
M. W. Anders
通讯作者：
M. W. Anders