Synthesis and Analysis of modified tRNA bases

修饰tRNA碱基的合成与分析

• 批准号: 5448193
• 负责人: Professor Dr. Thomas Carell
• 金额: --
• 依托单位: Department Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5448193?language=en
• 关键词: Synthesis; Analysis; modified; tRNA; bases

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.

非编码RNA分子如核糖体RNA，特别是转运RNA在细胞中具有核心重要性。这些RNA分子中的许多是化学高度修饰的。因此，RNA分子在标准碱基旁边含有大量修饰的碱基。通常这些修饰碱基的确切化学结构是未知的。此外，生物合成途径和所涉及的酶只是初步了解。在该项目的第一部分中，我们计划破译高度修饰的基础甘露糖基奎奥苷的化学结构。这将通过从猪肝中分离天然产物，NMR光谱分析，然后进行全合成来实现。该项目第二部分的目的是破译产生高度修饰的碱基ms2i6A的中心生化途径。我们认为存在一种未知的基于自由基的酶机制。这两个部分通过类似的合成和生物有机程序连接，并且这两个部分都处理位于许多tRNA的反密码子环中的高度修饰的RNA碱基的结构。

项目成果

Synthesis of RNA Containing 5-Hydroxymethyl-, 5-Formyl-, and 5-Carboxycytidine.

• DOI: 10.1002/chem.201704216
• 发表时间: 2017-11
• 期刊: Chemistry
• 作者: Iacovos N Michaelides;Nobuhiro Tago;Bastien Viverge;T. Carell