Triplex DNA structures

Frank-Kamenetskii, M.D. Mirkin, S.M. (1995) Triplex DNA structures. Annu. Rev. Biochem. 64, 65-95. 

Small Molecules that Stabilize Triplex DNA Structures... 

In rarer cases the ODNs also prevent normal gene transcription by directly forming triplex-helix structures with target DNA. This does not destroy a gene but prevents its unwinding or its binding to a gene promoter. 

The formation of three-stranded nucleic acid complexes was first demonstrated over five decades ago [56] but the possible biological role of an extended triplex was expanded by the discovery of the H-DNA structure in natural DNA samples [57-59]. H-DNA is an intermolecular triplex that is generally of the pyrimidine-purine x pyrimidine type ( dot -Watson-Crick pairing and cross Hoogsteen base paring) and can be formed at mirror repeat sequences in supercoiled plasmids [59]. 

A typical series of electropherograms is shown in Figure 13. In this context it should be noted that triplex DNA/PNA structures were also found... 

The presence of ions not only affects canonical base pairs [22], but promotes the formation of triplexes and other non-canonical DNA structures [23]. The effects of these interactions span from modifications of the renaturation kinetics of thermally denaturated DNA [24] to the known anti-tumoral and mutagenic activity of cisplatin [25]. 

A novel fluorinated polycyclic quinoacridinium cation RHPS4 (7) demonstrates enhanced binding to higher ordered DNA structures (triplex/quadru-plex) and has been shown to induce telomere shortening with an IC50 value of... 

Figure 4.7. Representations of some unusual higher order DNA structures triple helix (triplex), in which a third DNA strand hydrogen-bonds in the major groove of a double-stranded DNA a hairpin, in which a single strand of DNA hydrogen-bonds with itself to make a stem and nonpaired bases are pushed out to form a loop a tetraplex (quadruplex), in which (in this case) a single strand of DNA folds over on itself in an unusual G-G-G-G hydrogen bonding pattern, important in telomeric structure at the ends of chromosomes and a Holliday junction, in which four single strands of DNA base pair as usual but form this unusual complex structure, believed to be a good model for DNA recombination.

Tetraplex (= quadruplex) DNA (Fig. 4.9 and 4.12) has also been a target for detection by photophysical probes. The fluorescence of the dye DODC (see above) was found to be quenched by hairpin tetraplex DNA but not single-stranded DNA, duplex DNA, or parallel-stranded tetraplexes [326]. However, a later study found that triplex DNA competed very well with tetraplex DNA for DODC binding [322], The nature of the binding of DODC to these nucleic acid structures has not been clarified [322, 326]. 

Abstract The physical aspects of DNA structure and function are overviewed. Major DNA structures are described, which include the canonical Watson-Crick double helix (B form), B , A, Z duplex forms, parallel-stranded DNA, triplexes and quadruplexes. Theoretical models, which are used to treat DNA, are considered with special emphasis on the elastic-rod model. DNA topology, supercoiling and their biological significance are extensively discussed. Recent developments in the understanding of molecular interactions responsible for the stability of the DNA double helix are presented. 

Figure 2. Various DNA structures, (a) B-DNA (b) Z-DNA (c) intennolecular triplex (d) cruciform (e) H-DNA (intramolecular triplex) (f) G-quadruplex and its various foldings.

Recently, Chairs analyzed the oxazolium pentamethine cyanine dye 35 (DODC, Fig. 14.8) in DNA binding studies utilizing his competitive dialysis method [75]. The nucleic acid structures included single-stranded, duplex, triplex, and tetraplex forms. The comparative assay demonstrated that DODC binds to triplex DNA more selectively than any of the tetraplex forms included in the assay. In addition, the... 

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