Structure and stability of a DNA triple helix in solution: NMR studies on d(T)6.cntdot.d(A)6.cntdot.d(T)6 and its complex with a minor groove binding drug

Umemoto, Kimiko; Sarma, Mukti H.; Gupta, Goutam; Luo, Jianyang; Sarma, Ramaswamy H.

doi:10.1021/ja00167a063

Cited by 71 publications

(38 citation statements)

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“…Although several nmr investigations have been made (22,23,25,(49)(50)(51)(52)(53)(54)(55) on the triple helical structures, the helix type has been characterized in only two cases (22,23,51 ). The NOE cross peaks were analyzed for the interaction between the base H6/H8 and the sugar H2', H2~.…”

Section: Comparison With Triple Helical Models From Fiber Diffractionmentioning

confidence: 99%

Molecular Dynamics Investigations of DNA Triple Helical Models: Unique Features of the Watson-Crick Duplex

Sekharudu

Yathindra

Sundaralingam

1993

Journal of Biomolecular Structure and Dynamics

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We have built computer models of triple helical structures with a third poly(dT) strand Hoogsteen base paired to the major groove of a poly(dA).poly(dT) Watson-Crick (WC) base-paired duplex in the canonical A-DNA as well as B-DNA. For the A-DNA form, the sugar-phosphate backbone of the third strand intertwines and clashes with the poly(dA) strand requiring a radical alteration of the duplex to access the hydrogen bonding sites in the major groove. In contrast, when the duplex was in the canonical B-DNA form, the third strand was readily accommodated in the major groove without perturbing the duplex. The triple helical model, with the duplex in the B-DNA form, was equilibrated for 400ps using molecular dynamics simulations including water molecules and counter-ions. During the entire simulations, the deoxyriboses of the adenine strand oscillate between the S-type and E-type conformations. However, 30% of the sugars of the thymine strands-II & III switch to the N-type conformation early in the simulations but return to the S-type conformation after 200ps. In the equilibrium structure, the WC duplex portion of the triplex is unique and its geometry differs from both the A- or B-DNA. the deoxyriboses of the three strands predominantly exhibit S-type conformation. Besides the sugar pucker, the major groove width and the base-tilt are analogous to B-DNA, while the X-displacement and helical twist resemble A-DNA, giving a unique structure to the triplex and the Watson & Crick and Hoogsteen duplexes.

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Section: Comparison With Triple Helical Models From Fiber Diffractionmentioning

confidence: 99%

Molecular Dynamics Investigations of DNA Triple Helical Models: Unique Features of the Watson-Crick Duplex

Sekharudu

Yathindra

Sundaralingam

1993

Journal of Biomolecular Structure and Dynamics

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“…In such studies, purine and pyrimidine strand concentrations of 1:2 molar ratio have been used. The second pyrimidine strand is parallel to the purine strand and forms Hoogsteen base-pairing with the standard antiparallel Watson-Crick R:Y double helical DNA (16)(17)(18)(19)(20). A different class of triplexes are single-stranded oligonucleotide sequences that form intramolecular triple-stranded structures with well defined strand orientations (21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

NMR characterisation of a triple stranded complex formed by homo-purine and homo-pyrimidine DNA strands at 1:1 molar ratio and acidic pH

Bhaumik¹,

Chary²,

Govil³

et al. 1995

Nucl Acids Res

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Homo-purine (d-TGAGGAAAGAAGGT) and homopyrimidine (d-CTCCT TI CTTCC) oligomers have been designed such that they are complementary in parallel orientation. When mixed in a 1:1 molar ratio, the system adopts an antiparallel duplex at neutral pH with three mismatched base pairs. On lowering the pH below 5.5, a new complex is formed. The NMR results show the coexistence of a intermolecular pyrimidine.purine:pyrimidine DNA triplex and a single stranded oligopurine at this pH.

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“…The overall data base provided by these studies contains comparatively little information about triplexes containing purine third strands [e.g., RNA(purine)*RNA(purine)'DNA(pyrimidine)] compared with those containing pyrimidine third strands. Significantly, these studies find that triplex formation favors RNA in both pyrimidine strands and DNA in the purine strand, with no report of either a DNA(pyrimidine) RNA(purine) ligands as part of efforts to modulate the properties of triplex structures (15)(16)(17)(18)(19)(20)(21)(22)(23). However, those studies only assessed the impact of ligand binding on the properties of preformed triplexes.…”

mentioning

confidence: 99%

Ligand-induced formation of nucleic acid triple helices.

Pilch

Breslauer²

1994

Proc. Natl. Acad. Sci. U.S.A.

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We demonstrate that ligand binding can be used to induce the formation oftriplex structures that would not otherwise form. Speifically, we show that binding of berenil or 4',6-damd 2-phenylindole (DAPI) induces formation of the poy(rA) poly(rA) poy(dT) triplex, providing an example of an RNA(purine)RNA(purine)DNA(pyrimidine) triplex. We also show that binding of berenil, DAPI, ethidium, or ligands as part of efforts to modulate the properties of triplex structures (15-23). However, those studies only assessed the impact of ligand binding on the properties of preformed triplexes. This report provides an example of the use of ligand binding to induce formation of triple helices that would otherwise not form. The ability ofligands to alter dramatically the affinity and specificity of third strands for their double-helical targets opens the door to the design of novel antisense, antigene, and diagnostic strategies.To evaluate the influence of nucleic acid-binding ligands on intermolecular triplexes, we have studied the effects of berenil [1,3-bis(4'-amidinophenyl)triazene], 4',6-diamidino-2-phenylindole (DAPI), ethidium bromide (EtdBr), and netropsin (Fig. 1) *To whom reprint requests should be addressed. 9332The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Structure and stability of a DNA triple helix in solution: NMR studies on d(T)6.cntdot.d(A)6.cntdot.d(T)6 and its complex with a minor groove binding drug

Cited by 71 publications

References 0 publications

Molecular Dynamics Investigations of DNA Triple Helical Models: Unique Features of the Watson-Crick Duplex

Molecular Dynamics Investigations of DNA Triple Helical Models: Unique Features of the Watson-Crick Duplex

NMR characterisation of a triple stranded complex formed by homo-purine and homo-pyrimidine DNA strands at 1:1 molar ratio and acidic pH

Ligand-induced formation of nucleic acid triple helices.

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