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Postdoctoral position as posted on PostdocJobs.com:

http://www.PostdocJobs.com
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FTIs/RFIs: Development of a Unique Class of Cancer Chemotherapeutics

Our goal is to develop novel inhibitors of Ras to form the basis of
effective disease treatments by blocking its action in cellular signal
transduction cascades. Covalent modification of Ras with the farnesyl
lipid of farnesyl pyrophosphate (FPP) by the enzyme protein
farnesyltransferase (FTase) is essential for its oncogenic function.
Potent inhibitors of FTase (FTIs) have been developed and a number
have shown promise as anti-neoplastic agents in clinical trials.
However, isoforms of Ras, most notably K-Ras, evade the action of FTIs
because it can be alternatively modified by the related prenyl
transferase GGTase I, which is not inhibited by FTIs. Ras Function
Inhibitors (RFIs) are an alternative approach to blocking Ras function
by modifying the structure of the farnesyl lipid to interfere with
downstream aspects of Ras processing or metabolism.

Based upon promising initial results, we propose the hypothesis that
prenylation of Ras proteins with unnatural prenyl analogs will lead to
significant, biologically relevant effects on the activity of the
modified protein, and that these unnatural analogs will be lead
compounds for novel therapeutic agents. Two research avenues are
currently being pursued: 1) To synthesize structurally diverse
farnesyl pyrophosphate analogs using combinatorial methods to generate
new RFIs; 2) to characterize these molecules is a series of high
throughput biochemical and cellular based screens for anti-Ras
activity. This work will identify and define the molecular features of
unnatural FPP analogs that give rise to anti-Ras activity and lay the
foundation for future clinical therapy development.

Postdoctoral positions open:

1.Organic Synthesis: Synthesis of libraries of farnesyl and
geranylgeranyl pyrophosphate analogues via combinatorial and solid
phase synthesis.

2.Ras Biochemistry: Biological characterization of a novel class of
anti-cancer compounds (Ras function inhibitors). Projects focus on
defining the mechanism of RFI action, developing additional
anti-cancer agents, and examining the in vivo function of protein
isoprenylation.


For more information, please visit the Postdoc Jobs website:

http://www.PostdocJobs.com