Yang X L, Sugiyama H, Ikeda S, Saito I, Wang A H
Department of Cell and Structural Biology, University of Illinois, Urbana-Champaign 61801, USA.
Biophys J. 1998 Sep;75(3):1163-71. doi: 10.1016/S0006-3495(98)74035-4.
Isoguanine (2-hydroxyladenine) is a product of oxidative damage to DNA and has been shown to cause mutation. It is also a potent inducer of parallel-stranded DNA duplex structure. The structure of the parallel-stranded DNA duplex (PS-duplex) 5'-d(TiGiCAiCiGiGAiCT) + 5'-d(ACGTGCCTGA), containing the isoguanine (iG) and 5-methyl-isocytosine (iC) bases, has been determined by NMR refinement. All imino protons associated with the iG:C, G:iC, and A:T (except the two terminal A:T) basepairs are observed at 2 degrees C, consistent with the formation of a stable duplex suggested by the earlier Tm measurements [Sugiyama, H., S. Ikeda, and I. Saito. 1996. J. Am. Chem. Soc. 118:9994-9995]. All basepairs are in the reverse Watson-Crick configuration. The structural characteristics of the refined PS-duplex are different from those of B-DNA. The PS duplex has two grooves with similar width (7.0 A) and depth (7.7 A), in contrast to the two distinct grooves (major groove width 11.7 A, depth 8.5 A, and minor groove width 5.7 A, depth 7.5 A) of B-DNA. The resonances of the amino protons of iG and C are clearly resolved and observable, but those of the G and iC are very broad and difficult to observe. Several intercalators with different complexities, including ethidium, daunorubicin, and nogalamycin, have been used to probe the flexibility of the backbone of the (iG, iC)-containing PS-duplex. All of them produce drug-induced UV/vis spectra identical to their respective spectra when bound to B-DNA, suggesting that those drugs bind to the (iG, iC)-containing PS-duplex using similar intercalation processes. The results may be useful in the design of intercalator-conjugated oligonucleotides for antisense applications. The study presented in this paper augments our understanding of a growing number of parallel-stranded DNA structures, including the G-quartet, the i-motif, and the unusual homo basepaired parallel-stranded double helix. Their possible relevance is discussed.
异鸟嘌呤（2-羟基腺嘌呤）是DNA氧化损伤的产物，已被证明会导致突变。它也是平行链DNA双链结构的有效诱导剂。含有异鸟嘌呤（iG）和5-甲基异胞嘧啶（iC）碱基的平行链DNA双链体（PS-双链体）5'-d（TiGiCAiCiGiGAiCT）+5'-d（ACGTGCCTGA）的结构已通过NMR精修确定。在2℃时观察到与iG:C、G:iC和A:T（除了两个末端A:T）碱基对相关的所有亚氨基质子，这与早期熔点测量结果表明形成稳定双链体一致[Sugiyama, H., S. Ikeda, and I. Saito. 1996. J. Am. Chem. Soc. 118:9994-9995]。所有碱基对均处于反向沃森-克里克构型。精修后的PS-双链体的结构特征与B-DNA不同。PS-双链体有两条宽度（7.0 Å）和深度（7.7 Å）相似的沟槽，而B-DNA有两条不同的沟槽（大沟宽度11.7 Å，深度8.5 Å，小沟宽度5.7 Å，深度7.5 Å）。iG和C的氨基质子的共振清晰可辨且可观察到，但G和iC的共振非常宽且难以观察到。几种具有不同复杂性的嵌入剂，包括乙锭、柔红霉素和诺加霉素，已被用于探测含（iG，iC）的PS-双链体主链的柔韧性。当它们与B-DNA结合时，所有这些嵌入剂产生的药物诱导紫外/可见光谱与各自的光谱相同，这表明这些药物通过类似的嵌入过程与含（iG，iC）的PS-双链体结合。这些结果可能有助于设计用于反义应用的嵌入剂缀合寡核苷酸。本文提出的研究增进了我们对越来越多平行链DNA结构的理解，包括G-四联体、i-基序和不寻常的同型碱基配对平行链双螺旋。讨论了它们可能的相关性。
