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Title:Drug discovery against malaria parasite: drug repositioning strategy
Author(s):No, Joo Hwan
Director of Research:Oldfield, Eric
Doctoral Committee Chair(s):Oldfield, Eric
Doctoral Committee Member(s):Gennis, Robert B.; Baranger, Anne M.; Mitchell, Douglas A.
Department / Program:School of Molecular & Cell Bio
Discipline:Biophysics & Computnl Biology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Drug discovery
Malaria
Abstract:Malaria, caused by Plasmodium spp., causes ~1 million deaths each year and there are ever present problems due to drug resistance. In this work, I used drug-repositioning strategy with bisphosphonates to discover a lead that is active against malaria in vivo. The developmental procedures include, in vitro high throughput screening, x-ray crystallography and other biophysical techniques. First, a computational method was developed to elucidate the target of bisphosphonate in malaria parasite and, second, inhouse synthesized library of prenyl synthase inhibitors was used to find the lead, an analog of zoledronate, against the parasite, which the x-ray structure bound to target enzyme, farnesyl diphosphate synthase (FPPS), was solved. Also, the effect of lipophilic bisphosphonate against liver stage malaria parasite was investigated. Lastly, I studied the mechanism and inhibition of IspH, the last enzyme of nonmevalonate pathway, for discovery of a novel target for infectious disease.
Issue Date:2011-08-26
URI:http://hdl.handle.net/2142/26307
Rights Information:Copyright 2011 Joo Hwan No
Date Available in IDEALS:2011-08-26
2013-08-27
Date Deposited:2011-08


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