The Synthesis and Chemistry of Modified DNA Nucleobases

DNA包括典型的核碱基G、C、T和A，以及一些天然的、化学修饰的核碱基，包括5-甲基胞嘧啶、5-羟甲基胞嘧啶、5-甲酰胞嘧啶和5-羧胞嘧啶。该项目的总体目标是利用化学方法了解DNA中修饰核碱基的化学、发生率和功能。该项目的工作将涉及发展合成化学，以制备核苷、磷酰胺和由上述修饰碱基组成的单体的三磷酸衍生物。该项目的一部分将涉及合成除典型核碱基外还包括一个或多个修饰碱基的寡核苷酸。DNA的基本物理和化学性质，包括修改碱基将评估使用生物物理和光谱技术。该项目的另一个方面将涉及开发化学选择方法，在DNA链的背景下转化修饰的碱基，用于DNA中碱基修饰的检测和测序。

DNA comprises the canonical nucleobases G, C, T and A plus a number of natural, chemically modified nucleobases that include 5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine. The overall aims of the project are to understand the chemistry, the incidence and the function of modified nucleobases in DNA using chemical approaches. The project work will involve the development of synthetic chemistry to prepare nucleosides, phoshoramidites and triphosphate derivatives of monomers that comprise modified bases such as those mentioned. Part of the project will involve the synthesis of oligonucleotides that comprise one or more modified bases in addition to canonical nucleobases. The fundamental physical and chemical properties of DNA that includes modified bases will be evaluated using biophysical and spectroscopic techniques. Another aspect of the project will involve the development of chemoselective approaches for converting modified bases in the context of a DNA strand for applications that will include the detection and sequencing of base modification in DNA.