Analysis of Quadruplex Function in the Genome

DNA被认为主要以沃森-克里克双螺旋形式存在于活细胞中。越来越多的证据表明，DNA的折叠结构是动态的，其他结构形式可以存在并发挥作用。已知在某些富含G的DNA序列中形成的四链DNA/称为G-四链螺旋/可能存在于我们染色体的许多不同位置。有证据表明，四重螺旋的形成可以关闭某些基因。这一提议旨在探索这一假说以及设计选择性稳定这种四螺旋结构的分子的化学可能性，并通过这样做来影响某些基因的功能。这将代表着一种通过直接控制基因来改变生物功能的新的令人兴奋的方式。鉴于基因构成正常功能的基础，也是疾病的基础，该计划的总体目标有可能激发出新的治疗方法，通过选择性地针对DNA结构而不是蛋白质来应对人类疾病和状况。

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 alternative structural forms can exist and have function. 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 is likely to exist in 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 this hypothesis along with the chemical possibility of designing molecules that selectively stabilise such quadruple helix structures, and by doing so affect the function of certain genes. This would represent a new and exciting way to alter biological function by directly controlling genes. Given that genes form the basis for normal function and also for disease, the overall aims of this programme has the potential to inspire new therapeutic approaches to address human diseases and conditions by selectively targeting DNA structures, rather than proteins.