Brown H S, Shapiro R
Biochemistry. 1977 Mar 22;16(6):1229-35. doi: 10.1021/bi00625a031.
The conformations of 12 dinucleoside monophosphates containing N4-phenylcytidine (CPh) or N4(beta-naphthyl)cytidine (CbetaN) residues have been studied, using circular dichroic spectroscopy. The following compounds had aqueous spectra resembling their parent compounds, which lacked the modifying aromatic substituent: CPhpU, CbetaNpU, UpCPh, UpCbetaN, CPhpG, CbetaNpG, GpCPh, and CPhpA. The spectra of GpCbetaN and ApCbetaN were almost the reverse of the unmodified compounds, while CbetaNpA and ApCPh were intermediary in character. When the spectra were run in methanol, all major differences between the modified and unmodified compounds disappeared. This result suggested that the differences observed in aqueous solution were the result of stacking interactions between the aromatic ring and a neighboring purine. When the aromatic ring was naphthalene, the modified cytidine occupied the 3'-terminal position, and, when the purine was adenine, the effect was enhanced. These conclusions were supported by a consideration of chemical shifts in the 1H NMR spectra of ApCbetaN, and GpCbetaN, as compared to those of the unmodified compounds and CbetaNpG. A study of molecular models of ApCbetaN and GpCbetaN revealed a unique conformation in which the purine rotates to a syn position, in order to allow a close stacking interaction with the naphthalene ring. No such conformation is available for CbetaNpA and CbetaNpG, and the best partial stacking interaction occurs in a conformation with the purine in the anti conformation. The base-displacement theory of carcinogenesis (Levine, A. F., Fink, L. M., Weinstein, I. B., and Grunberger, D. (1974), Cancer Res. 34, 319) describes the conformational change resulting from the attachment of a bulky aromatic residue at the 8 position of guanine in RNA or DNA, and attributes biological importance to the event. The changes that occur upon substitution of the amino group of cytosine differ in detail from the above, but would be expected to produce similar biological results. Base-displacement effects need not be limited, therefore, to a particular substitution position in a nucleic acid.
利用圆二色光谱研究了12种含有N4-苯基胞苷（CPh）或N4（β-萘基）胞苷（CβN）残基的二核苷单磷酸的构象。以下化合物在水溶液中的光谱与其母体化合物相似，母体化合物缺乏修饰性芳基取代基：CPhpU、CβNpU、UpCPh、UpCβN、CPhpG、CβNpG、GpCPh和CPhpA。GpCβN和ApCβN的光谱几乎与未修饰化合物的光谱相反，而CβNpA和ApCPh的光谱具有中间特征。当在甲醇中测定光谱时，修饰和未修饰化合物之间的所有主要差异都消失了。这一结果表明，在水溶液中观察到的差异是芳环与相邻嘌呤之间堆积相互作用的结果。当芳环为萘时，修饰的胞苷占据3'-末端位置，当嘌呤为腺嘌呤时，这种效应会增强。与未修饰化合物和CβNpG相比，ApCβN和GpCβN的1H NMR光谱中的化学位移分析支持了这些结论。对ApCβN和GpCβN分子模型的研究揭示了一种独特的构象，其中嘌呤旋转到顺式位置，以便与萘环形成紧密的堆积相互作用。CβNpA和CβNpG没有这种构象，最佳的部分堆积相互作用发生在嘌呤处于反式构象的构象中。致癌作用的碱基位移理论（Levine, A. F., Fink, L. M., Weinstein, I. B., and Grunberger, D. (1974), Cancer Res. 34, 319）描述了由于在RNA或DNA中鸟嘌呤的8位连接一个庞大的芳基残基而导致的构象变化，并赋予该事件生物学重要性。胞嘧啶氨基取代时发生的变化在细节上与上述情况不同，但预计会产生类似的生物学结果。因此，碱基位移效应不必局限于核酸中的特定取代位置。
