Poppitt D G, Fox B W
Chem Biol Interact. 1975 Sep;11(3):163-71. doi: 10.1016/0009-2797(75)90096-4.
The interaction of the alkanesulphonate, methylene dimethanesulphonate (MDMS) with DNA has been studied. Thermal denaturation studies on mixtures of MDMS and DNA showed a dose-dependent decrease of the melting temperature midpoint (Tm) of the DNA. In addition, an irreversible decrease in ultraviolet absorption (hypochromism) preceded the hyperchromic shift, the magnitude of the former being linearly related to both the relative concentration of MDMS and the G-C content of the DNA used. Neither the reduction in melting temperature nor the initial UV absorption decrease occurred after dialysis of the reaction mixture. Equimolar proportions of the hydrolysis products of MDMS did not give the same effects as observed with the unhydrolysed agent. A similar hypochromism followed by strand separation occurs when DNA is allowed to stand with MDMS at room temperature, the time of subsequent strand separation being related to the treatment level of the drug. A weak association of MDMS with DNA is considered to be involved resulting in a local compression of the helical structure in the vicinity of the G-C pairs. It is suggested that this conformational change may act as a substrate for repair enzymes in vivo.
已对链烷磺酸盐——亚甲基二磺酸盐（MDMS）与DNA的相互作用进行了研究。对MDMS和DNA混合物的热变性研究表明，DNA的解链温度中点（Tm）呈剂量依赖性降低。此外，在增色位移之前出现了不可逆的紫外线吸收降低（减色效应），前者的幅度与MDMS的相对浓度以及所用DNA的G-C含量均呈线性相关。反应混合物透析后，解链温度降低和初始紫外线吸收降低均未出现。等摩尔比例的MDMS水解产物未产生与未水解试剂相同的效果。当DNA在室温下与MDMS放置时，会出现类似的减色效应，随后发生链分离，后续链分离的时间与药物的处理水平有关。认为MDMS与DNA存在弱结合，导致G-C对附近的螺旋结构局部压缩。有人提出，这种构象变化可能在体内作为修复酶的底物。
