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Oldfield, Eric Oldfield, Eric Gennis, Robert B. Baranger, Anne M. Mitchell, Douglas A. No, Joo Hwan 2011-08-26T15:22:19Z 2011-08-26T15:22:19Z 2013-08-27T10:00:21Z 2011-08-26T15:22:19Z 2011-08 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. Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2011-06-30T15:22:48Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 No_Joo Hwan.pdf: 18910996 bytes, checksum: 74e31ce436a361b8f90c02791abb5938 (MD5) Made available in DSpace on 2011-08-26T15:22:19Z (GMT). No. of bitstreams: 2 No_JooHwan.pdf: 18910996 bytes, checksum: 74e31ce436a361b8f90c02791abb5938 (MD5) license.txt: 4052 bytes, checksum: f7aaa15441bde78bdf988f24112ab886 (MD5) Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by William Ingram (wingram2@illinois.edu) on 2011-08-26T15:25:52Z Item is restricted until 2013-08-26T15:25:28Z Item reinstated by Sarah Shreeves (sshreeve@illinois.edu) on 2013-08-27T10:00:21Z Item was in collections: University of Illinois Dissertations and Theses (ID: 204) Dissertations - Biophysics and Computational Biology (ID: 689) No. of bitstreams: 2 No_JooHwan.pdf: 18910996 bytes, checksum: 74e31ce436a361b8f90c02791abb5938 (MD5) license.txt: 4052 bytes, checksum: f7aaa15441bde78bdf988f24112ab886 (MD5) Item released from any restrictions by Sarah Shreeves (sshreeve@illinois.edu) on 2013-08-27T10:00:21Z http://hdl.handle.net/2142/26307 en Copyright 2011 Joo Hwan No Drug discovery Malaria Drug discovery against malaria parasite: drug repositioning strategy School of Molecular & Cell Bio 1415 Biophysics & Computnl Biology 0319 University of Illinois at Urbana-Champaign Dissertation Ph.D. PHD:Biophys&Computnl Bio -UIUC 10KS0319PHD