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Full-Text Articles in Physical Sciences and Mathematics
Biomimetic Tools In Oxidative Metabolism: Characterization Of Reactive Metabolites From Antithyroid Drugs, Kudzanai Chipiso
Biomimetic Tools In Oxidative Metabolism: Characterization Of Reactive Metabolites From Antithyroid Drugs, Kudzanai Chipiso
Dissertations and Theses
Toxicities of sulfur-based drugs have been attributed to formation of highly reactive sulfur oxo-acids and depletion of glutathione by the formation of reactive metabolites. Metabolic activation of these sulfur centers to conceivably toxic reactive metabolites (RMs) that can covalently modify proteins is considered the initial step in drug-induced toxicity. Despite considerable effort and research, detection and characterization of these RMs during drug development and therapy remains a challenge. Methimazole (MMI) and 6-propyl-2-thiouracil (PTU) are two commonly used antithyroid, sulfur-based drugs. Though effective, these drugs are associated with idiosyncratic toxicity. PTU has acquired a black box warning and physicians are calling …
Enzymatic Control Of The Related Pathways Of Fatty Acid And Undecylprodiginine Biosynthesis In Streptomyces Coelicolor, Renu Singh
Dissertations and Theses
Streptomyces coelicolor produces fatty acids for both primary metabolism and for production of the components of natural products such as undecylprodiginine. Primary metabolism makes the longer and predominantly branched-chain fatty acids, while undecylprodiginine utilizes shorter and almost exclusively straight chain fatty acids. The first step in fatty acid biosynthetic process is catalyzed by FabH (β-ketoacyl synthase III), which catalyzes a decarboxylative condensation of an acyl-CoA primer with malonyl-acyl carrier protein (ACP). The resulting 3-ketoacyl-ACP product is reduced by NADPH-dependent FabG into 3-hydroxyacyl-ACP, which is dehydrated by FabA to form enoyl-ACP. The NADH-dependent FabI (InhA) completes the cycle. Subsequent rounds of …
Biosynthesis Of Marineosin, A Spiroaminal Undecylprodiginine Natural Product, Shaimaa Mohamed Salem
Biosynthesis Of Marineosin, A Spiroaminal Undecylprodiginine Natural Product, Shaimaa Mohamed Salem
Dissertations and Theses
Marineosins A and B are two spiroaminal-ring containing tripyrrole compounds isolated from the marine actinomycete, Streptomyces CNQ-617, and were found to possess potent and selective cytotoxic activity against leukemia and melanoma. Marineosins belong to the prodiginines class of natural products, examples of which are undecylprodiginine and streptorubin B. Unlike marineosins, prodiginines structures are characterized by the presence of fully conjugated tripyrrole nucleus linked to an alkyl chain (that lacks any oxygen). Cyclic prodiginines arise from an oxidative cyclization of the alkyl chain onto the tripyrrole, a step catalyzed by Rieske-oxygenase like enzymes such as RedG. The biosynthesis of prodiginines is …