Synthesis and Analysis of modified tRNA bases

非编码RNA分子，如核糖体RNA，特别是转移RNA，在细胞中是至关重要的。这些RNA分子中的许多都经过了化学高度修饰。因此，RNA分子除了标准碱基外，还含有各种各样的修饰碱基。通常这些修饰过的碱基的确切化学结构是未知的。此外，生物合成途径和涉及的酶只是初步了解。在项目的第一部分，我们计划破译超修饰的甘露糖基基苷的化学结构。这将通过从猪肝中分离天然产物，核磁共振光谱分析，然后全合成来实现。该项目第二部分的目的是破译产生超修饰碱基ms2i6A的主要生化途径。我们认为存在一种未知的基于自由基的酶机制。这两个部分是通过类似的合成和生物有机程序连接起来的，两个部分都处理位于许多trna反密码子环中的超修饰RNA碱基的结构。

Non-coding RNA molecules such as ribosomal RNA and in particular transfer RNA are of central importance in cells. Many of these RNA molecules are chemical highly modified. As such, the RNA molecules contain next to the standard bases a large variety of modified bases. Often the exact chemical structures of these modified bases are unknown. In addition, the biosynthetic pathways and the involved enzymes are only rudimentarily understood. In the first part of the project, we plan to decipher the chemical structure of the hypermodified base mannosylqueuosine. This will be achieved by isolation of the natural product from pork liver, NMR spectroscopic analysis, followed by total synthesis. The aim of the second part of the project is to decipher the central biochemical pathway that gives rise to the hypermodified base ms2i6A. We believe the existence of an unknown radical-based enzyme mechanism. Both parts are linked by similar synthetic and bioorganic procedures and both parts deal with the structure of hypermodified RNA bases that are situated in the anticodon loop of many tRNAs.