Balasubramanian Shankar
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
Bioorg Med Chem. 2014 Aug 15;22(16):4356-70. doi: 10.1016/j.bmc.2014.05.016. Epub 2014 May 15.
In this article I discuss studies towards understanding the structure and function of DNA in the context of genomes from the perspective of a chemist. The first area I describe concerns the studies that led to the invention and subsequent development of a method for sequencing DNA on a genome scale at high speed and low cost, now known as Solexa/Illumina sequencing. The second theme will feature the four-stranded DNA structure known as a G-quadruplex with a focus on its fundamental properties, its presence in cellular genomic DNA and the prospects for targeting such a structure in cels with small molecules. The final topic for discussion is naturally occurring chemically modified DNA bases with an emphasis on chemistry for decoding (or sequencing) such modifications in genomic DNA. The genome is a fruitful topic to be further elucidated by the creation and application of chemical approaches.
在本文中,我将从化学家的视角探讨关于在基因组背景下理解DNA结构与功能的研究。我所描述的第一个领域涉及那些促成一种高速、低成本在基因组规模上对DNA进行测序的方法的发明及后续发展的研究,该方法如今被称为Solexa/Illumina测序。第二个主题将聚焦于一种名为G-四链体的四链DNA结构,重点关注其基本特性、在细胞基因组DNA中的存在情况以及利用小分子靶向细胞中这种结构的前景。最后一个讨论主题是天然存在的化学修饰DNA碱基,着重于用于解码(或测序)基因组DNA中此类修饰的化学方法。基因组是一个通过化学方法的创建与应用有待进一步阐明的丰富主题。