Investigating pathogen 4Fe-4S protein targets and cancer chemotherapies with bisphosphonate/diphosphate inhibitors

The broad, long-term objective of this research is to develop drug leads for new antibiotics, antiparasitics, and cancer chemotherapeutics. Two main areas of focus are inhibition of the Methyl Erythritol Phosphate (MEP; non-mevalonate pathway) pathway in bacterial and parasitic human pathogens and inhibition of isoprenoid synthases in human cancers. For the development of antibacterials and antiparasitics, this research investigates the structure, function, and inhibition of the essential penultimate and ultimate enzymes of the MEP pathway, IspG (iron sulfur protein G; also known as GcpE and E-4-hydroxy-2-C-methyl-erythritol pyrophosphate synthase) and IspH (also know as LytB and E-4-hydroxy-2-C-methyl-erythritol pyrophosphate reductase), respectively. Investigation of novel cancer drugs focuses on mono- and combination therapies targeting the farnesyl pyrophosphate synthase (FPPS) and GGPPS (geranyl geranyl pyrophosphate synthase) enzymes with drugs that interact with several pathways involved in autophagy and apoptosis.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics & Computnl Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Guerra, Francisco

Contributors dc:contributor

• Oldfield, Eric
• Nair, Satish K.
• Gennis, Robert B.
• Gruebele, Martin

• isoprenoid
• iron-sulfur proteins
• 4Fe-4S
• bisphosphonate
• diphosphate

Statement dc:rights

• Copyright 2014 Francisco Guerra

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/72983

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/72983