{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/85470"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/85470","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Experimental and Computational Study of Bisphosphonates Targeting Isoprenoid Biosynthesis Pathway","abstract":"Bisphosphonates are a class of drugs widely used to treat bone resorption diseases. Recently, bisphosphonates have been found to have anti-cancer, anti-parasitic, anti-bacterial and herbicidal activity. They also have the unexpected property of activating human gammadelta T cells to kill tumor cells. In this work, I used experimental, mainly x-ray crystallography and computational methods to understand the structure activity relationships of these bisphosphonates with their targets, farnesyl diphosphate synthase, geranylgeranyl diphosphate synthase, and undecaprenyl diphosphate synthase. New bisphosphonates have been developed and optimized based on these findings. In particular, new lipophilic bisphosphonates targeting multiple prenyl-transferases are developed and far more potent than current commercially available bisphosphonate drugs in tumor cell killing, and gammadelta T cell activation.","abstract_html":"Bisphosphonates are a class of drugs widely used to treat bone resorption diseases. Recently, bisphosphonates have been found to have anti-cancer, anti-parasitic, anti-bacterial and herbicidal activity. They also have the unexpected property of activating human gammadelta T cells to kill tumor cells. In this work, I used experimental, mainly x-ray crystallography and computational methods to understand the structure activity relationships of these bisphosphonates with their targets, farnesyl diphosphate synthase, geranylgeranyl diphosphate synthase, and undecaprenyl diphosphate synthase. New bisphosphonates have been developed and optimized based on these findings. In particular, new lipophilic bisphosphonates targeting multiple prenyl-transferases are developed and far more potent than current commercially available bisphosphonate drugs in tumor cell killing, and gammadelta T cell activation.","abstract_has_math":false,"creators":["Cao, Rong"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biophysics and Computational Biology","degree_department":null,"school":null,"contributors":["Oldfield, Eric"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-09-25T22:46:12Z","date_published":"2015-09-25T22:46:12Z","updated_at":"2026-07-22T22:26:25Z","subjects":["Health Sciences, Oncology"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(MiAaPQ)AAI3337715"],"render_values":[{"text":"(MiAaPQ)AAI3337715","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/85470","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Oldfield, Eric"]},{"key":"dc:creator","label":"Author","values":["Cao, Rong"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-09-25T22:46:12Z","10000-01-01","2008"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biophysics and Computational 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":["Health Sciences, Oncology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/85470","(MiAaPQ)AAI3337715"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Bisphosphonates are a class of drugs widely used to treat bone resorption diseases. Recently, bisphosphonates have been found to have anti-cancer, anti-parasitic, anti-bacterial and herbicidal activity. They also have the unexpected property of activating human gammadelta T cells to kill tumor cells. In this work, I used experimental, mainly x-ray crystallography and computational methods to understand the structure activity relationships of these bisphosphonates with their targets, farnesyl diphosphate synthase, geranylgeranyl diphosphate synthase, and undecaprenyl diphosphate synthase. New bisphosphonates have been developed and optimized based on these findings. In particular, new lipophilic bisphosphonates targeting multiple prenyl-transferases are developed and far more potent than current commercially available bisphosphonate drugs in tumor cell killing, and gammadelta T cell activation.","Made available in DSpace on 2015-09-25T22:46:12Z (GMT). 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Recently, bisphosphonates have been found to have anti-cancer, anti-parasitic, anti-bacterial and herbicidal activity. They also have the unexpected property of activating human gammadelta T cells to kill tumor cells. In this work, I used experimental, mainly x-ray crystallography and computational methods to understand the structure activity relationships of these bisphosphonates with their targets, farnesyl diphosphate synthase, geranylgeranyl diphosphate synthase, and undecaprenyl diphosphate synthase. New bisphosphonates have been developed and optimized based on these findings. In particular, new lipophilic bisphosphonates targeting multiple prenyl-transferases are developed and far more potent than current commercially available bisphosphonate drugs in tumor cell killing, and gammadelta T cell activation.","Made available in DSpace on 2015-09-25T22:46:12Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 3337715.pdf: 2724603 bytes, checksum: 00143008892fdac7c230b8f83a49e9e1 (MD5) Previous issue date: 2008","Embargo set by: Seth Robbins for item 86751 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","180 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008."],"dc:identifier":["http://hdl.handle.net/2142/85470","(MiAaPQ)AAI3337715"],"dc:language":["eng"],"dc:subject":["Health Sciences, Oncology"],"dc:title":["Experimental and Computational Study of Bisphosphonates Targeting Isoprenoid Biosynthesis Pathway"],"dc:type":["text"],"thesis:degree_discipline":["Biophysics and Computational Biology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:25Z"}