[10]1H NMR spectroscopy of DNA triplexes and quadruplexes

Feigon, Juli; Koshlap, Karl M.; Smith, Flint W.

doi:10.1016/s0076-6879(95)61012-x

Cited by 124 publications

(108 citation statements)

References 70 publications

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“…Thus, in the absence of K ϩ , T30695 appears to assume a standard alternating syn-anti-syn-anti G-quartet conformation. This conformation has been observed for other intra-and inter-molecular G-quartets, most notably the analogous intra-molecular G-quartet that has been studied by Feigon and colleagues (20). According to the NOE-based analysis of G-quartet structure (20), the NOEs observed between G n H8 and G n H2Ј, H2Љ (for all 8 G residues in the G-quartets) also match the syn-anti-synanti G-quartet structure for the central core.…”

Section: Resultssupporting

confidence: 60%

“…The NOE cross-peaks between base H8 and H1Ј protons play a key role in the determination of G-quartet structure since they can be used to establish angles for the bases. Strong H8 -H1Ј NOEs were observed for residues G2, G6, G10, and G14, from which we conclude that they assume the syn-conformation in the central G-octet (20). Weak NOE peaks between G2H8-G3H1Ј, G6H8-G7H1Ј, G10H8-G11H1Ј, and G14H8-G15H1Ј and medium NOEs between G11H8-G10H1Ј and G15H8-G14H1Ј are consistent with an anti-conformation for those bases.…”

Section: Resultssupporting

confidence: 59%

“…Non-exchangeable proton resonances were identified in NOESY in D 2 O and the exchangeable resonances were assigned by model-independent quartet assignment. These resonances were used when interpreting through-space connectivity to find assignments (20). Sequence-specific assignments of non-exchangeable resonances were obtained by analyses of NOESY spectra and 1 H-31 P COSY.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Structure-Activity of Tetrad-forming Oligonucleotides as a Potent Anti-HIV Therapeutic Drug

Ning¹,

Hogan²

1998

Journal of Biological Chemistry

156

124

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Recently, we have described the design and characterization of oligonucleotides containing only G and T bases, i.e. T30695 and T30177, that are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in culture (Jing, N., Rando, R. F., Pommier, Y., and Hogan, M. E. (1997) Biochemistry 36, 12498 -12505). To understand that observation and to rationalize the generally high thermal stability of oligonucleotide folding for these compounds, we have used NMR methods, coupled to molecular modeling, to obtain a high resolution structure model for T30695, which is the most potent of the integrase inhibitors that have been identified thus far. Modeling and NMR data obtained in the presence of Li ؉ ions show that T30695 assumes an intramolecular fold with a distorted G-octet core and a set of three open, partially disordered loops. This is referred to as Li ؉ -form structure. The NMR-based model suggests that, upon coordination with three K ؉ equivalents, the central G-octet becomes more regular and that the loop domains become orderly and compact. This is referred to as K ؉ -form structure. Based upon the assay of inhibition of HIV-1 integrase, T30695 demonstrated a strong inhibition of HIV-1 integrase activity as the K ؉ -form structure, but a poor inhibition of HIV-1 integrase activity as the Li ؉ -form structure. The structure/activity analysis suggests that the K ؉ -induced conformation transition of the tetrad-forming oligonucleotides, such as T30695 and T30177, plays a key role in inhibition of HIV-1 integrase activity.Integration of HIV-1 1 viral DNA into a host chromosome is an essential step for its replication (1). As the only enzyme required for HIV-1 integration, integrase catalyzes the insertion of HIV-1 viral DNA into the host genome in a two-step reaction. First, integrase cleaves two nucleotides from the 3Ј-end of the linear proviral DNA. Then, upon binding to the proviral duplex, integrase catalyzes the covalent coupling of the cleaved 3Ј-end to a site of the host chromosome, which had been nicked by the integrase (1-3). Since it is critical to HIV-1 viral replication, integrase has become an attractive target for selective anti-HIV therapies. Pharmaceutical inhibition of HIV-1 integration has been reported for 3Ј-azido-3Ј-deoxythymidine (4), deoxyriboses with substitution or unsaturation at the 3Ј-position (5), tyrphostins (6), cosalane analogues (7), and triplex-forming oligonucleotides (8). All of the candidates mentioned above had an IC 50 in the micromolar range for inhibition of the strand transfer or the terminal exonuclease activity, which is too high to be of general utility.Recently, a new class of oligonucleotides was developed to be an inhibitor of HIV-1 integrase (9). The most potent anti-HIV-1 oligonucleotide in this oligomer family was reported to be a 17-mer (T30177), 5Ј-g*tggtgggtgggtggg*t, synthesized with two phosphorothioate linkages (one at each end). According to preliminary physical analysis, it was proposed that T30177 formed an intramolecular G-quartet structu...

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Section: Resultssupporting

confidence: 60%

Section: Resultssupporting

confidence: 59%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Structure-Activity of Tetrad-forming Oligonucleotides as a Potent Anti-HIV Therapeutic Drug

Ning¹,

Hogan²

1998

Journal of Biological Chemistry

156

124

View full text Add to dashboard Cite

show abstract

“…The C4 H6-H5 NOE and COSY cross-peaks were observed in spectra recorded at 7°C. I3 base H8 to H1' NOE shows intensity comparable to that of H5 to H6 NOEs of C. or cross-strand NOEs, which have been observed in DNA triplexes (Dittrich et al, 1994;reviewed by Radhakrishnan & Patel, 1995) and quadruplexes (reviewed by Feigon et al, 1995). While present in duplex forms at physiologically relevant conditions, conformational transitions have been detected for CGG repeats at temperatures below 20°C and for GAC repeats at pH < 7.0.…”

Section: Homo-duplex Formation and Antiglycosidic Orientation Of Basesmentioning

confidence: 73%

Genetically Unstable CXG Repeats are Structurally Dynamic and Have a High Propensity for Folding. An NMR and UV Spectroscopic Study

Zheng

Huang

Smith

et al. 1996

Journal of Molecular Biology

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“…In contrast to the Watson-Crick base pairing that exhibits chemical shift of 13-14 ppm for guanine imino protons (H 1 ) (25), the typical chemical shifts for the guanine imino proton involved G-G pairing were within the range of 10 -12 ppm (26,27). In the absence of potassium ion, the guanine imino protons of WNT1 DNA showed several typical chemical shifts at around 13 ppm (Fig.…”

Section: The G-rich Sequence Located At the Wnt1 Promoter Is Capable mentioning

confidence: 95%

Inhibition of Cancer Cell Migration and Invasion through Suppressing the Wnt1-mediating Signal Pathway by G-quadruplex Structure Stabilizers

Wang¹,

Huang

Kuo

et al. 2014

Journal of Biological Chemistry

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Background:The Wnt1 pathway is recognized to play a major role in cancer progression. Results: The promoter region of the WNT1 gene can form G-quadruplex structures, which regulate WNT1 expression and its downstream signaling pathways. Conclusion: The Wnt1-mediated migration and invasion activities of cancer cells are inhibited by G-quadruplex stabilizers. Significance: A pathway-specific strategy is identified to repress cancer metastasis using G-quadruplex stabilizers.

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[10]1H NMR spectroscopy of DNA triplexes and quadruplexes

Cited by 124 publications

References 70 publications

Structure-Activity of Tetrad-forming Oligonucleotides as a Potent Anti-HIV Therapeutic Drug

Structure-Activity of Tetrad-forming Oligonucleotides as a Potent Anti-HIV Therapeutic Drug

Genetically Unstable CXG Repeats are Structurally Dynamic and Have a High Propensity for Folding. An NMR and UV Spectroscopic Study

Inhibition of Cancer Cell Migration and Invasion through Suppressing the Wnt1-mediating Signal Pathway by G-quadruplex Structure Stabilizers

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