Protein farnesylation is a post translational modification of proteins catalyzed by
protein farnesyltransferases (pFTase), and involves attachment of a farnesyl (15
carbons) isoprenoid moiety to a C-terminal residue of protein containing a CAAX-box
motif, where C is cysteine, A is an aliphatic amino acid, and X is a specific amino acid
that controls the isoprenoid moiety addition1. The high site specificity of pFTase and
its moderate tolerance of subtle changes in farnesyl moiety make farnesylation a
valuable method of protein immobilization, and a novel tool for analyzing proteinprotein
interactions in chemical biology3. During spring of 2011, I worked on synthesis
of a novel farnesyl analogue containing a formylbenzoate moiety and characterized
its effectiveness with pFTase to be used in further experimentation in protein
immobilization by a Ph. D. candidate, Mohammad Rashidian. The novel farnesyl
analogue, Geranyl FormylBenzoate Pyrophosphate (GFBPP), was optimized from
original multistep synthesis of seven reactions to five reactions with dramatic
increase in final product yield from 5.6% to 14%. Enzymatic evaluation of GFBPP
with pFTase showed higher affinity of enzyme to GFBPP at the cost of slower
reaction rate. GFBPP was later evaluated as an analogue for rapid reversible protein
immobilization using pFTase by Mr. Rashidian.
Additional contributors: Mohammad Rashidian; Dr. Mark Distefano (faculty mentor)
Synthesis and Applications of Site- Specific Analogue of Farnesyltransferase in Reversible Immobilization.
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