Quadruplex recognition and discrimination by dynamic combinatorial chemistry

动态组合化学的四联体识别和区分

• 批准号: BB/E013481/1
• 负责人: Sir Shankar Balasubramanian
• 金额: $ 42.24万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE013481%2F1
• 关键词: Quadruplex; recognition; discrimination; dynamic; combinatorial

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.

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，并且可以存在各种替代的结构形式。有一种四股DNA /一种四股螺旋，称为G-四股螺旋/已知在某些富含G的DNA序列中形成，已知存在于我们染色体的许多不同位置。有证据支持四重螺旋的形成可以关闭某些基因。该提议旨在探索产生小分子配体的可能性，所述小分子配体可以通过靶向对于每个四链体似乎是独特的环结构来特异性地识别这样的四链体。从长远来看，这可能会导致一类新的治疗药物，其功能是选择性地靶向DNA二级结构而不是蛋白质。