Synthesis and Analysis of modified tRNA bases

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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.