Drug discovery against malaria parasite: drug repositioning strategy

No, Joo Hwan

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

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

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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