The Synthesis and Chemistry of Modified DNA Nucleobases

DNA包含典型的核碱基G、C、T和A加上许多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-甲酰基胞嘧啶和5-羧基胞嘧啶。该项目的总体目标是利用化学方法了解DNA中修饰的核碱基的化学、发生率和功能。该项目的工作将涉及合成化学的发展，以制备核苷，亚磷酰胺和三磷酸衍生物的单体，包括修饰的碱基，如那些提到的。该项目的一部分将涉及合成的寡核苷酸，其中包括一个或多个修饰的碱基，除了典型的核碱基。将使用生物物理和光谱技术评估包括修饰碱基的DNA的基本物理和化学性质。该项目的另一个方面将涉及开发化学选择性方法，用于在DNA链的背景下转换修饰的碱基，用于包括DNA中碱基修饰的检测和测序的应用。

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.