Development of New Chemical Approaches for Diagnostic Medicine and for Syntheses of Antibacterial Agents

Totaro, Kyle A.

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Year:: 2014
Contributor:: Totaro, Kyle A (creator); Sello, Jason (Director); Basu, Amit (Reader); Delaney, Sarah (Reader); Brown University. Chemistry (sponsor)
Genre:: theses
Subject:: Diagnostic Medicine; Diversity-Oriented Synthesis; Multicomponent Reactions; Rational Design; Antibacterial agents; Mycobacterium tuberculosis
Extent:: xvii, 421 p.
DOI: https://doi.org/10.7301/Z0NC5ZJD

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Abstract:: Medicine can be divided into two central components: the diagnosis of a disease and its treatment. Both components of medicine are being transformed by the availability of new “omics” technologies in which gene, proteins, and metabolites are holistically analyzed and measured. At the center of these “omics” technologies are the principles of chemistry and ingeniously designed chemical reagents. It is my contention that chemistry will continue to play a critical role in the diagnosis and treatment of disease. The work in this thesis describes new chemical methods for disease diagnosis via metabolomics and the synthesis of antibacterial drug candidates identified via genomics. We demonstrate that a multicomponent reaction can be used to chemoselectively derivatize a wide range of metabolites, including amino acids, neurotransmitters, hormones, intermediates in central metabolism, and co-factors. The potential of this technology for disease diagnosis is highlighted in the derivatization and detection of metabolites associated with the metabolic disorder, Phenylketonuria. While it also describes the development of new methodologies for the syntheses of peptide antibiotics discovered in a traditional screen for antibacterial agents, this thesis illustrates how “omics” technologies can inform antibacterial drug discovery and development. Specifically, it depicts the rational design and synthesis of species-selective inhibitors of the mycobacterial proteasome, a tuberculosis drug target identified via state-of-the art genomic approaches. Collectively, the results in the thesis illustrate how chemistry can be transformative in both disease diagnosis and drug development.
Notes:: Thesis (Ph.D. -- Brown University (2014)

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Rights: In Copyright
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Citation

Totaro, Kyle A., "Development of New Chemical Approaches for Diagnostic Medicine and for Syntheses of Antibacterial Agents" (2014). Chemistry Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z0NC5ZJD

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Chemistry Theses and Dissertations

Theses and Dissertations for the Chemistry department.
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