GQ: Guanine-Quartets/Quadruplexes

The grand-polymer, DNA, has been produced an immense refinement of ideas about a plethora of its structural diversity beyond the first most reported double helical structure half-century back. The Watson-Crick B-form double helix, one of a large number of stable structures that DNA can form, however, seem to be functionally limited. In contrast, non-B DNA structures with different helical sense, different number of strands, and alternative base interactions have been discovered (such as curved, cruciformed, triplex, quadruplex; approximately one new DNA form every 2 years in the past 4 decades) and known to relate to various aspects of biological functions.

We are interested in DNA sequences of guanine (G)-rich tracts which could assume secondary-structures known as guanine (G)-quadruplexes. When four guanine bases are close enough together they could form planer hydrogen-bonded arrangements, called guanine quartets (G-quartets), a non-B type DNA structure with a cyclic and square-planer arrays of four paired guanine bases where each unit donates two Hoogsteen-type hydrogen bonds to one neighbor and receives two hydrogen bonds from the other neighbor (see Fig. below).

In addition to their intense biological role in vivo, their tendency for self-assembly (self-aggregation) towards higher-ordered supramolecular structures making them distinct for autonomously construction of bio-nano-architectures and thus their significant role from nanotechnology to medicinal chemistry.

 

             We investigated the molecular determinates and self-assembling behavior of a series of simple G-rich oligonucleotides (GROs) using gel electrophoresis, CD, AFM and NMR methods. A group of sequences were discovered to generate ultra-stable aggregates bearable against the denaturants and nucleases which are further being investigated to use in bio- and nano-technologies.