Author

Ke-wei Chang

Graduation Semester and Year

2015

Language

English

Document Type

Thesis

Degree Name

Master of Science in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Frank W Foss

Abstract

Transfer ribonucleic acids (tRNAs) from all organisms contain modified nucleosides, which are derived from four different nucleosides. Research has indicated that tRNA modifications affect translation and various metabolic pathways. Among these modifications, some of them need more than one enzyme to produce specific nucleosides. Researchers are interested in investigating the fundamental mechanisms and function of post-transcriptional modifying enzymes. A number of these enzymes are metal-dependent, such as MiaB and MiaE. MiaE enzyme (2-methylthio-N6-isopentenyl-adenosine(37)-tRNA monooxygenase) stereospecifically hydroxylates an adeonosine derivative at the 37th position of tRNA, ms2i6A37, to complete the hypermodification of 2-methylthio-N6-(4-hydroxyisopentenyl)-adenosine (ms2io6A37). Several studies showed that the ms2io6A37 modification of tRNA seems to influence the central metabolic pathways. Therefore, in order to study the biological activity of iron-dependent enzymes, such as MiaE, or other enzymes with radical mechanisms. We planned to synthesize spin-labeled analogs of ms2io6A37, the substrate of MiaE. Chapter 1 describes the background of tRNA modifications and the MiaA, MiaB, and MiaE pathway for A37 modification in bacterial tRNA. Chapter 2 shows different strategies to synthesize the desired nucleoside spin probe. Chapter 3 proposes several reactions to improve this synthesis in the future. Last, chapter 4 provides the experimental details used in this project to help other chemists to investigate the modified ribose spin-label chemistry.

Keywords

MiaE, Spin-label

Disciplines

Chemistry | Physical Sciences and Mathematics

Comments

Degree granted by The University of Texas at Arlington

25437-2.zip (1789 kB)

Included in

Chemistry Commons

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