Michael W. Amolins1, Andrew Placzek2, and Richard Gibbs2. (1) Augustana College, Sioux Falls, SD, (2) Purdue University, West Lafayette, IN
A series of deuterium-labeled isoprenoids were synthesized both for a group in the Netherlands studying mevalonate kinase deficiencies and for a Purdue University group studying farnesyltransferase inhibitors used for the prevention of cancer. Among them were 3-vinyl CD3-but-2(E)-ene-1-diphosphate (or 3-CD3-dimethylallyl pyrophosphate), 3-vinyl CD3-7-methylocta-2(E),6(E)-diene-1-diphosphate (or 3-CD3-geranyl pyrophosphate), 3-Vinyl CD3-7,11-dimethyldodeca-2(E),6(E),10-triene-1-diphosphate (or 3-CD3-farnesyl pyrophosphate), and 3-vinyl CD3-7,11,15-trimethylhexadeca-2(E),6(E),10(E),14-tetraene-1-diphosphate (or 3-CD3-geranylgeranyl pyrophosphate), each of which are compounds found along the mevalonate pathway. The Netherlands study, using tandem mass spectrometry as an analytical tool, will utilize the isotopically labeled isoprenoids as internal standards to determine fluctuation in the isoprenoid biosynthesis of cultured cells collected from patients. This, in turn, will provide a semi-diagnostic method of identifying enzyme defects along the pathway. In addition, the compounds will be used as part of a study to identify which signaling pathways and individual proteins play a role in the auto-inflammatory diseases associated with mevalonate kinase deficiency. Purdue will use a similar analytical method to study the physiological aspects of protein prenylation and its applications to cancer prevention.
Web Page:
www.mcmp.purdue.edu/faculty/?uid=rag
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