Quadruplex recognition and discrimination by dynamic combinatorial chemistry

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DNA is presumed to exist largely as the Watson-Crick double helix in living cells. There is growing evidence to suggest that the folded structure of DNA is dynamic and that various alternative structural forms can exist. There is a four stranded form of DNA / a quadruplex helix called a G-quadruplex / that is known to form in certain G-rich sequences of DNA known to exist is many different places in our chromosomes. There is evidence to support that the formation of the quadruple helix can switch 'off' certain genes. This proposal aims to explore the possibility of generating small molecule ligands that can specifically recognise such quadruplexes by targeting loop structures that appear to be unique for each quadruplex. This might in the longer term lead to a new class of therapeutic agents that function by selectively targeting DNA secondary structures rather than proteins.