Rational Design of Novel Irreversible Inhibitors for Human Arginase and Applications of Nanoparticles for Catalytic Reactions

Guo, Xuefeng

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Year:: 2019
Contributor:: Guo, Xuefeng (creator); Seto, Christopher (Advisor); Basu, Amit (Reader); Sun, Shouheng (Reader); Brown University. Department of Chemistry (sponsor)
Genre:: theses
Subject:: Catalysis; Mass spectrometry; Pharmaceutical chemistry; Organic compounds--Synthesis; Pharmacokinetics
Extent:: xiii, 172 p.
DOI: https://doi.org/10.26300/2pc0-mf46

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Abstract:: Parasites have developed a variety of strategies for invading hosts and escaping their immune response. A common mechanism by which parasites escape nitric oxide (NO) toxicity is the activation of host arginase. This activation leads to a depletion of L-arginine, which is the substrate for NO synthase, resulting in lower levels of NO and increased production of polyamines that are necessary for parasite growth and differentiation. For this reason, small molecule inhibitors for arginase show promise as new anti-parasitic chemotherapeutics. The first part of this thesis describes the discovery of novel irreversible arginase inhibitors, and their characterization using biochemical, kinetic, and structural studies. Data from tandem mass spectrometry shows that the inhibitor occupies the enzyme active site and forms a covalent bond with Thr135 of arginase. These findings pave the way for the development of more potent and selective irreversible arginase inhibitors. Catalytic science is central to the chemical and energy industries. The recent push for sustainable chemistry has intensified research to identify active, stable and economically accessible catalysts for chemical reactions. Highly controlled nanoparticles can provide a uniform environment with each nanoparticle being exposed on the surface to maximize catalysis efficiency. The second part of this thesis describes the syntheses of several nanoparticles and utilizing them for catalyzing multiple organic reactions, such as dehalogenation reactions, one-pot syntheses of benzoxazoles and quinazolines, and polymerization reactions. The innovative heterogeneous catalysis and synthesis methods in this study provide a new platform for catalyzing reactions with optimum efficiency and provide new insights into the advanced catalytic systems for future applications.
Notes:: Thesis (Ph. D.)--Brown University, 2019

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Guo, Xuefeng, "Rational Design of Novel Irreversible Inhibitors for Human Arginase and Applications of Nanoparticles for Catalytic Reactions" (2019). Chemistry Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/2pc0-mf46

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Chemistry Theses and Dissertations

Theses and Dissertations for the Chemistry department.
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