Structural studies of a stable parallel-stranded DNA duplex incorporating isoguanine: Cytosine and isocytosine: Guanine basepairs by nuclear magnetic resonance spectroscopy

Xiang Lei Yang, Hiroshi Sugiyama, Shuji Ikeda, Isao Saito, Andrew H.J. Wang

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57 引文 斯高帕斯(Scopus)

摘要

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°C, consistent with the formation of a stable duplex suggested by the earlier T(m) 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 Å) and depth (7.7 Å), in contrast to the two distinct grooves (major groove width 11.7 Å, depth 8.5 Å, and minor groove width 5.7 Å, depth 7.5 Å) 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.

原文英語
頁(從 - 到)1163-1171
頁數9
期刊Biophysical Journal
75
發行號3
DOIs
出版狀態已發佈 - 9月 1998
對外發佈

ASJC Scopus subject areas

  • 生物物理學

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