Ganguly Manjori, Wang Feng, Kaushik Mahima, Stone Michael P, Marky Luis A, Gold Barry
Eppley Institute for Research in Cancer, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE-68198-6025, USA.
Nucleic Acids Res. 2007;35(18):6181-95. doi: 10.1093/nar/gkm670. Epub 2007 Sep 12.
The incorporation of 7-deazaguanine modifications into DNA is frequently used to probe protein recognition of H-bonding information in the major groove of DNA. While it is generally assumed that 7-deazaguanine forms a normal Watson-Crick base pair with cytosine, detailed thermodynamic and structural analyses of this modification have not been reported. The replacement of the 7-N atom on guanine with a C-H, alters the electronic properties of the heterocycle and eliminates a major groove cation-binding site that could affect the organization of salts and water in the major groove. We report herein the characterization of synthetic DNA oligomers containing 7-deazaguanine using a variety of complementary approaches: UV thermal melting, differential scanning calorimetry (DSC), circular dichroism (CD), chemical probing and NMR. The results indicate that the incorporation of a 7-deazaguanine modification has a significant effect on the dynamic structure of the DNA at the flanking residue. This appears to be mediated by changes in hydration and cation organization.
将7-脱氮鸟嘌呤修饰掺入DNA中常用于探测蛋白质对DNA大沟中氢键信息的识别。虽然通常认为7-脱氮鸟嘌呤与胞嘧啶形成正常的沃森-克里克碱基对，但尚未见对这种修饰进行详细的热力学和结构分析的报道。用C-H取代鸟嘌呤上的7-N原子，改变了杂环的电子性质，并消除了一个可能影响大沟中盐和水的组织的大沟阳离子结合位点。我们在此报告使用多种互补方法对含有7-脱氮鸟嘌呤的合成DNA寡聚物进行的表征：紫外热变性、差示扫描量热法（DSC）、圆二色性（CD）、化学探针法和核磁共振（NMR）。结果表明，7-脱氮鸟嘌呤修饰的掺入对侧翼残基处DNA的动态结构有显著影响。这似乎是由水合作用和阳离子组织的变化介导的。
