2'-deoxy-7-(hydroxymethyl)-7-deazaadenosine: A new analogue to model structural water in the major groove of DNA
2'-deoxy-7-(hydroxymethyl)-7-deazaadenosine: A new analogue to model structural water in the major groove of DNA
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DOI：
10.1021/ja961540s
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发表时间：
1996-10-23
影响因子：
15
通讯作者：
Gumport, RI
中科院分区：
文献类型：
--
作者：
Rockhill, JK;Wilson, SR;Gumport, RI
合成了一种新的脱氧核苷，2 ′-脱氧-7-（羟甲基）-7-脱氮腺苷，目的是利用类似物来模拟DNA大沟中“结构"沃茨的作用。以2-（（乙氧基亚甲基）氨基）-5-溴-1-（2 ′-脱氧-3 ′，5 ′-二-O-对甲苯酰基-β-D-赤型-戊呋喃糖基）吡咯-3，4-二甲腈为起始原料，分四步合成目标化合物。通过X射线衍射和质子核磁共振波谱分析表征了其结构。晶体结构显示N6上的氨基质子与羟甲基的氧之间存在分子内氢键。当叠加到色氨酸（trp）阻遏物/操纵基因复合物结构中的特定腺嘌呤上时，类似物将羟甲基的氧放置在非常靠近蛋白质/DNA复合物中水贡献的氧的位置。这种类似物可能是有用的探测结构沃茨在其他特定的蛋白质/DNA复合物和DNA弯曲的作用。
A novel deoxynucleoside, 2'-deoxy-7-(hydroxymethyl)-7-deazaadenosine, was synthesized with the intent of using the analogue to mimic the role of ''structural'' waters in the major groove of DNA. The target compound was synthesized in four steps starting from 2-((ethoxymethylene)amino)-5-bromo-1-(2'-deoxy-3',5'-di-O-p-toluoyl-beta-D-erythro-pentofuranosyl)pyrrole-3,4-dicarbonitrile. The structure was characterized by X-ray diffraction and proton NMR spectroscopic analyses. The crystal structure shows an intramolecular hydrogen bond between an amino proton on N6 and the oxygen of the hydroxymethyl group. When superimposed onto particular adenines in the structure of the tryptophan (trp) repressor/operator complex, the analogue places the oxygen of the hydroxymethyl group very near the oxygen contributed by the water in the protein/DNA complex. This analogue may be useful for probing the role of structural waters in other specific protein/DNA complexes and in DNA bending.