MECHANISM OF HYDROXYLAMINE MUTAGENESIS - TAUTOMERIC SHIFTS AND PROTON-EXCHANGE BETWEEN THE PROMUTAGEN N6-METHOXYADENOSINE AND CYTIDINE
MECHANISM OF HYDROXYLAMINE MUTAGENESIS - TAUTOMERIC SHIFTS AND PROTON-EXCHANGE BETWEEN THE PROMUTAGEN N6-METHOXYADENOSINE AND CYTIDINE
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DOI：
10.1021/bi00388a022
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发表时间：
1987-07-14
期刊：
影响因子：
2.9
通讯作者：
SHUGAR, D
中科院分区：
文献类型：
--
作者：
STOLARSKI, R;KIERDASZUK, B;SHUGAR, D
鉴于诱变剂N6-甲氧基腺苷(OMe6A)的氨基而不是亚氨基与潜在互补的尿苷[Stolarski，R.，Kierdaszuk，B.，Hagberg，C.-E.和Shugar，D.(1984)BioChemical 23,2913]形成平面构型(碱基对)，现在已经发现，借助1H核磁共振光谱技术，只有OMe6A的亚氨基互变构体与潜在的互补胞苷配对。这种杂相缔合物的缔合常数比OMe6A的自缔合常数高一个数量级以上。异构体的形成伴随着OMe6A互变异构平衡的显著变化，氨基形式的数量从18%增加到高达44%，而亚胺物种的数量相应减少。此外，胞苷在OMe6A溶液中的存在显著提高了两种互变异构体之间的互变速率。胞苷与OMe6A的亚氨基形成平面杂化缔合物。用饱和转移法测定了不同浓度和温度下的交换速率常数和互变异构体交换速率常数。提出了一个质子交换模型，该模型考虑了互变异构体交换和质子交换的相互依赖，以及自缔合物和异构体的作用。简要讨论了这些结果与羟胺和甲氧胺诱变的分子基础以及其他体系中的质子交换现象的关系。
Whereas the amino, but not imino, tautomer of the promutagen N6-methoxyadenosine (OMe6A) forms planar associates (base pairs) with the potentially complementary uridine [Stolarski, R., Kierdaszuk, B., Hagberg, C.-E., and Shugar, D. (1984) Biochemistry 23, 2913], it has now been found, with the aid of 1H NMR spectroscopic techniques, that only the imino tautomer of OMe6A base pairs with the potentially complementary cytidine. The association constant for such heteroassociates is more than an order of magnitude higher than that for autoassociates of OMe6A. The formation of heteroassociates is accompanied by a marked shift in tautomeric equilibrium of OMe6A, with an increase in the population of the amino form from 18% to as high as 44% and a corresponding decrease in the population of the imino species. Furthermore, the presence of cytidine in a solution of OMe6A appreciably enhances the rate of tautomeric exchange between the two tautomeric forms. Formation of planar heteroassociates between cytidine and the imino form of OMe6A. The rate constants for this exchange and for tautomeric exchange, determined by the saturation transfer technique, have been measured at various concentrations and temperatures. A model is advanced for proton exchange that takes into account the interdependence of tautomeric exchange and proton exchange, as well as the role of auto- and heteroassociates. The relevance of these results to the molecular basis of hydroxylamine and methoxyamine mutagenesis and to the phenomenon of proton exchange in other systems is briefly discussed.