TY - JOUR
T1 - Structural studies of a stable parallel-stranded DNA duplex incorporating isoguanine
T2 - Cytosine and isocytosine: Guanine basepairs by nuclear magnetic resonance spectroscopy
AU - Yang, Xiang Lei
AU - Sugiyama, Hiroshi
AU - Ikeda, Shuji
AU - Saito, Isao
AU - Wang, Andrew H.J.
N1 - Funding Information:
This work was supported by National Institutes of Health Grant GM41612 (to A.H.-J.W.) and by a grant from CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation (JST) (to H.S.). The Varian VXR500 NMR spectrometer work at the University of Illinois at Urbana-Champaign was supported in part by the National Institutes of Health Shared Instrumentation Grant 1S10RR06243. The 750 MHz NMR spectra were obtained in the Varian Oxford Instrument Center for Excellence in their NMR Laboratory. Funding for this instrumentation was provided in part by the W. M. Keck Foundation, the National Institutes of Health (Grant PHS 1 S10RR10444–01), and the National Science Foundation (NSF CHE 96–10502).
PY - 1998/9
Y1 - 1998/9
N2 - 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.
AB - 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.
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U2 - 10.1016/S0006-3495(98)74035-4
DO - 10.1016/S0006-3495(98)74035-4
M3 - Article
C2 - 9726918
AN - SCOPUS:0031660471
SN - 0006-3495
VL - 75
SP - 1163
EP - 1171
JO - Biophysical Journal
JF - Biophysical Journal
IS - 3
ER -