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Title:Isoprenoid Biosynthesis Pathway as a Drug Target for Bisphosphonates: Transcriptional Profile Investigation
Author(s):Leon-Rossell, Annette
Doctoral Committee Chair(s):Oldfield, Eric
Department / Program:Biophysics and Computational Biology
Discipline:Biophysics and Computational Biology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Biophysics, General
Abstract:Bisphosphonates are known as potent inhibitors of the enzyme farnesyl diphosphate synthase (FPPS) and are clinically used to treat bone related disorders such as osteoporosis and bone cancer. Here we describe the development, testing and study of the mechanism of action of novel bisphosphonates as anti-bacterial and anti-cancer agents. We identified a FPPS bisphosphonate inhibitor which in combination with the phosphonate drug fosmidomycin exerted a potent synergistic effect in Escherichia coli. Additionally, we designed novel groups of bisphosphonates which are ∼10-1000 fold more potent against tumor cell lines than conventional bisphosphonates due to their ability to inhibit more than one enzyme in the mevalonate pathway.
Issue Date:2007
Type:Text
Language:English
Description:158 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2007.
URI:http://hdl.handle.net/2142/85459
Other Identifier(s):(MiAaPQ)AAI3269961
Date Available in IDEALS:2015-09-25
Date Deposited:2007


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