Molecular Engineering of Guanine-Rich Sequences: Z-DNA, DNA Triplexes, and G-Quadruplexes

Guanine's array of hydrogen bond donors and acceptors lead it to take part in structures as diverse as B-DNA, Z-DNA, hairpins, cruciforms, triplexes, and G-quadruplexes. These structures, though varied, are closely related, and guanine-rich oligonucleotides can often participate in equilibria among several different assemblies. In contrast to the right-handed helix of B-type DNA, Z-DNA forms a left-handed helix in which the base pairs are located nearly perpendicular to the phosphate backbone. Triple helices are formed when a single-stranded triplexforming oligonucleotide (TFO) binds in the major groove of double-stranded DNA (dsDNA). Depending on the orientation of the TFO relative to the homopurine strand of the dsDNA, triplexes can be classified as either parallel or antiparallel. Four guanines can self-assemble through the formation of eight. Hoogsteen hydrogen bonds and form a guanine or G-tetrad.