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Identification Of Human Topoisomerase I Poison And Catalytic Inhibitors, Christian Madeira

FIU Electronic Theses and Dissertations

Inhibition of human topoisomerase I have been shown to reduce excessive transcription of PAMP-induced genes based on prior studies, which offers a solution to offset complications of sepsis such as tissue damage and organ failure. The enzyme resolves the topological constraints on DNA that encodes these genes. The aim of this study is to identify human topoisomerase I (HTop1) inhibitors that can a.) prevent the relaxation of negative supercoiled plasmid DNA by HTop1 and b.) reduce HTop1 binding to DNA and formation of covalent cleavage complex (HTop1cc) utilizing a novel yeast screening system. Top hits from in-silico screening conducted by …