Triple-helical DNA

A few recent NMR investigations of polynucleotides include studies of triple-helical DNA,689 Holliday junctions,290 double-stranded oligonucleotides containing adducts of carcinogens,690 691 of hairpin loops with sheared A A and G G pairs,692 and of proton exchange in both imino and amino groups.693... 

Fig. 6.3. Structure of triple helical DNA. An oligonucleotide bound to a double-stranded DNA molecnle.

There are three grooves in triple-helical DNA which can be targeted for binding by ligands either covalently or noncovalently. The third strand of a triplex is positioned asymmetrically in the major groove and the vacant minor... 

Figure 4,8. Hoogsten hydrogen bonding that leads to triple helical DNA AT-T (top) and GC-C+ (bottom). The third base, a pyrimidine, fits into the major groove of double helical DNA.

Figure 4.32. Schematic of triple helical DNA formation monitored by FRET. The substitution of GC by TA to form a mismatch in the triplex was detected in this study. [From Fig. 2 of Ref. 323, with permission.]...

Biochemical Connections Draw the interactions between bases that make triple-helical DNA possible. 

E. coli. Phospholipase C, also a metalloenzyme, can also be inhibited by aminoglycosides. Inhibition of dopamine regulating P-type Ca channels by neomycin can also be considered a toxic pathway. Lastly, aminoglycosides have been shown to bind triple-helical DNA, which are known to exist in biological systems as potential regulators of gene expression. ... 

The Hoogsteen hydrogen bonding motif between cytidine and adenine (shown below) requires that the cytidine be protonated, and in fact as the pH is lowered below 7 to between 5 and 6, triple helical DNA formation is enhanced. 

Moser H.E., Dervan P.B. Sequence-specific cleavage of double helical DNA by triple helix formation. Science 1987 238 645-650. 

Abstract Protoberberine alkaloids and related compounds represent an important class of molecules and have attracted recent attention for their various pharmacological activities. This chapter deals with the physicochemical properties of several isoquinoline alkaloids (berberine, palmatine and coralyne) and many of their derivatives under various environmental conditions. The interaction of these compounds with polymorphic DNA structures (B-form, Z-form, H -form, protonated form, triple helical form and quadruplex form) and polymorphic RNA structures (A-form, protonated form, triple helical form and quadruplex form) reported by several research groups, employing various analytical techniques such as spectrophotometry, spectrofluorimetry, circular dichro-ism, NMR spectroscopy, viscometry as well as molecular modelling and thermodynamic analysis to elucidate their mode and mechanism of action for structure-activity relationships, are also presented. 

Fig. 6.7 Simplified scheme of the copying process in DNA replication via triple helices, as described by Li and Nicolaou (Ferris, 1994)...

Figure 5-24 Proposed structure of H-DNA which can be formed when a homopyrimidine segment and its complementary homopurine segment separate as a result of protonation of the cytosine rings or of negative supercoiling stress.239,240 The triple-helical portion contains base triplets of the kind shown in Fig. 5-7.

Figure 5-25 Two superposed stereoscopic diagrams illustrating the lowest energy triple helical conformations of one pyrimidine, one purine, and one Hoogsteen DNA strand (in black). Superposed is an RNA purine strand in gray. See Srinivasan and Olson.238 Courtesy of Wilma K. Olson.

An alternative approach is to synthesize highly specific hydrolysis-resistant DNA analogs that can form triple helical structures with DNA (Chapter 5). 

Roberts, R. W., and D. M. Crothers, Stability and properties of double and triple helices Dramatic effects of RNA or DNA backbone composition. Science 258 1463-1466,... 

The stacking of nucleobases has been found to be involved in several DNA self-assembly processes, promoting the formation of DNA-DNA and DNA-protein complexes in vivo [44, 45], driving end-to-end interactions of DNA double- and triple-helices in semi-dilute solutions [46], or determining the geometry of DNA... 

---