{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/26307"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/26307","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Drug discovery against malaria parasite: drug repositioning strategy","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.","abstract_html":"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.","abstract_has_math":false,"creators":["No, Joo Hwan"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biophysics & Computnl Biology","degree_department":null,"school":null,"contributors":["Oldfield, Eric","Gennis, Robert B.","Baranger, Anne M.","Mitchell, Douglas A."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-08-26T15:22:19Z","date_published":"2011-08-26T15:22:19Z","updated_at":"2026-07-22T22:25:26Z","subjects":["Drug discovery","Malaria"],"languages":["en"],"rights":["Copyright 2011 Joo Hwan No"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/26307","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Oldfield, Eric","Gennis, Robert B.","Baranger, Anne M.","Mitchell, Douglas A."]},{"key":"dc:creator","label":"Author","values":["No, Joo Hwan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-08-26T15:22:19Z","2013-08-27T10:00:21Z","2011-08"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biophysics & Computnl Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Drug discovery","Malaria"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2011 Joo Hwan No"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/26307"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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"]},{"key":"dc:title","label":"Title","values":["Drug discovery against malaria parasite: drug repositioning strategy"]}]}],"canonical_facts":{"dc:contributor":["Oldfield, Eric","Gennis, Robert B.","Baranger, Anne M.","Mitchell, Douglas A."],"dc:creator":["No, Joo Hwan"],"dc:date":["2011-08-26T15:22:19Z","2013-08-27T10:00:21Z","2011-08"],"dc:description":["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"],"dc:identifier":["http://hdl.handle.net/2142/26307"],"dc:language":["en"],"dc:rights":["Copyright 2011 Joo Hwan No"],"dc:subject":["Drug discovery","Malaria"],"dc:title":["Drug discovery against malaria parasite: drug repositioning strategy"],"thesis:degree_discipline":["Biophysics & Computnl Biology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:26Z"}