University of Illinois Urbana-Champaign

Drug discovery against malaria parasite: drug repositioning strategy

No, Joo Hwan

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No_JooHwan.pdf

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https://hdl.handle.net/2142/26307

Description

Title
Drug discovery against malaria parasite: drug repositioning strategy
Author(s)
No, Joo Hwan
Issue Date
2011-08-26T15:22:19Z
Director of Research (if dissertation) or Advisor (if thesis)
Oldfield, Eric
Doctoral Committee Chair(s)
Oldfield, Eric
Committee Member(s)
  • Gennis, Robert B.
  • Baranger, Anne M.
  • Mitchell, Douglas A.
Department of Study
School of Molecular & Cell Bio
Discipline
Biophysics & Computnl Biology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2011-08-26T15:22:19Z
Keyword(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.
Graduation Semester
2011-08
Permalink
http://hdl.handle.net/2142/26307
Copyright and License Information
Copyright 2011 Joo Hwan No

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