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Wed, 15 Jun 2011 08:47:41 -0400 |
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George Mason University |
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To: Biology Graduate Students < [log in to unmask]>,
Bioinformatics students < [log in to unmask]>,
Anna Baranova < [log in to unmask]>, Daniel N Cox < [log in to unmask]>,
Alan H Christensen < [log in to unmask]>,
Chip Petricoin < [log in to unmask]>,
Geraldine M Grant < [log in to unmask]>,
Karl J Fryxell < [log in to unmask]>,
Monique Van Hoek < [log in to unmask]>, Yuntao Wu < [log in to unmask]>,
Charles L Bailey < [log in to unmask]>, Jim Willett < [log in to unmask]>,
Serguei Popov < [log in to unmask]>, Lance Liotta < [log in to unmask]>,
Valery Soyfer < [log in to unmask]>,
Kylene Kehn-Hall < [log in to unmask]>,
Fatah Kashanchi < [log in to unmask]>,
Alessandra Luchini < [log in to unmask]>,
Ramin M Hakami < [log in to unmask]>,
[log in to unmask], Robin Couch < [log in to unmask]>
cc: Tiffany C Sandstrum < [log in to unmask]>,
Sarah Kostka < [log in to unmask]>, "Gail L. Hodges" < [log in to unmask]> |
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> *Thesis Defense Announcement
> To: The George Mason University Community*
>
> *Candidate: Elizabeth McKenney
> Program: Master of Science in Biology
> *
> *Date: Friday June 17, 2011
> Time: 11:00 a.m.
> Place: George Mason University, Prince William campus
> Bull Run Hall, Room 247
>
> Thesis Chair: Dr. Monique van Hoek
>
> Title: **"Analogs of Fosmidomycin and FR900098 as Antimicrobial Agents"*
>
>
>
> A copy of the thesis is on reserve in the Johnson Center Library,
> Fairfax campus. The thesis will not be read at the meeting, but
> should be read in advance.
>
> All members of the George Mason University community are invited to
> attend.
>
>
> ABSTRACT:
>
> Isoprenoids are involved in many critical cellular functions, such as
> cell wall and membrane biosynthesis and electron transport. Plants,
> fungi, and some bacteria use the methylerythritol phosphate (MEP)
> pathway to generate isoprenoids. Since the MEP pathway is absent in
> animals, enzymes of this pathway are attractive targets for the
> development of a novel class of antibiotics. Fosmidomycin and
> FR900098 are two antibiotics that are potent inhibitors of
> 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), the enzyme
> involved in the first committed step of the MEP pathway. Fosmidomycin
> is currently in clinical trials to treat infections of /Plasmodium
> falciparum/, the organism that causes malaria. Homologs of DXR have
> been identified in many bacteria, including /F. tularensis, E. coli,
> P. aeruginosa, B. abortus, /and /M. tuberculosis/. Fosmidomycin
> inhibits the purified DXR of /F. tularensis, E. coli, /and /M.
> tuberculosis/. The goal of this research was to identify and test
> analogs of fosmidomycin and FR900098 that are more lipophilic, and
> therefore theoretically able to cross biological membranes more
> efficiently. After screening a panel of compounds, we have identified
> one compound, termed EU195, which can inhibit the growth of
> /Francisella novicida/. Fosmidomycin, FR900098, and EU195 can also
> inhibit the intracellular growth of /F. novicida/ with low
> cytotoxicity. These antibiotics can also prolong the survival of
> /Galleria mellonella/ wax moth caterpillars that have been infected
> with /F. novicida/. This research shows that the lipophilic FR900098
> analog, EU195, may be a promising contribution to current antibiotics,
> and that further research in this area to improve these compounds
> would be beneficial.
>
> ###
>
>
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