Isoprenoid Biosynthesis Pathway as a Drug Target for Bisphosphonates: Transcriptional Profile Investigation

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics and Computational Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Leon-Rossell, Annette

Contributors dc:contributor

• Oldfield, Eric

• Biophysics, General

Language dc:language

eng

Identifier

(MiAaPQ)AAI3269961

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/85459