| Abstract
| - A number of biochemical processes rely on isoprenoids, including the post-translational modification ofsignaling proteins and the biosynthesis of a wide array of compounds. Photoactivatable analogues havebeen developed to study isoprenoid utilizing enzymes such as the isoprenoid synthases and prenyltransferases. While these initial analogues proved to be excellent structural analogues with good cross-linkingcapability, they lack the stability needed when the goals include isolation of cross-linked species, trypticdigestion, and subsequent peptide sequencing. Here, the synthesis of a benzophenone-based farnesyldiphosphate analogue containing a stable phosphonophosphate group is described. Inhibition kinetics,photolabeling experiments, as well as X-ray crystallographic analysis with a protein prenyltransferaseare described, verifying this compound as a good isoprenoid mimetic. In addition, the utility of this newanalogue was explored by using it to photoaffinity label crude protein extracts obtained from Heveabrasiliensis latex. Those experiments suggest that a small protein, rubber elongation factor, interactsdirectly with farnesyl diphosphate during rubber biosynthesis. These results indicate that this benzophenone-based isoprenoid analogue will be useful for identifying enzymes that utilize farnesyl diphosphate as asubstrate.
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