Publication Date

2016

Document Type

Dissertation/Thesis

First Advisor

Hagen, Timothy J.

Degree Name

Ph.D. (Doctor of Philosophy)

Department

Department of Chemistry and Biochemistry

LCSH

Enzyme inhibitors||Enzymes--Synthesis||Chemicals||Organic chemistry

Abstract

This dissertation focuses on four projects. In collaboration with Seattle Structural Genomics Center for Infectious Disease (SSGCID), FOL7185 was identified as a fragment hit that binds to IspD and IspE enzymes isolated from bacteria.1 The first project deals with the synthesis and biological activity of pyrazolopyrimidines that were synthesized based on FOL7185. The second project discusses the design, synthesis and biological evaluation of imidazole compounds. These compounds were designed and synthesized using template molecule FOL955, a fragment hit co-crystallized with Burkholderia pseudomallei (Bp) IspF (PDB code: 3QHD). 2 Moreover, this project also deals with the design and synthesis of a dansyl containing fluorescent compound and its activity against BpIspF. In the third project, we used FOL535 that was co-crystallized with BpIspF (PDB code: 3K14)2 as a starting point to design and synthesize imidazothiazole containing compounds. These compounds were designed and synthesized by replacing an ethyl ester with a variety substituents. In addition, this dissertation includes the synthesis and docking studies of regioisomers of FOL535 analogs that can engage the zinc and cytidine binding sites of BpIspF. In our BpIspF assay, L-tryptophan hydroxamate was used as a standard, however, the compound was not available from chemical vendors. The last project discusses the synthesis of L- and D-tryptophan hydroxamates in three steps from commercially available L- and D-tryptophan respectively.

Comments

Advisors: Timothy J. Hagen.||Committee members: Timothy J. Hagen; James R. Horn; Narayan S. Hosmane; Douglas A. Klumpp; Rangaswamy Meganathan.

Extent

303 pages

Language

eng

Publisher

Northern Illinois University

Rights Statement

In Copyright

Rights Statement 2

NIU theses are protected by copyright. They may be viewed from Huskie Commons for any purpose, but reproduction or distribution in any format is prohibited without the written permission of the authors.

Media Type

Text

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