Developing Technologies for Studying Protein Prenylation

Prenylation (the modification of proteins with the cholesterol biosynthesis intermediates C(15) fargeranylgeranyl) is a newly discovered postranslational modification that targets certain proteins tointerior of the cell, thereby regulating their biological activity. The best studied example illustrmodification is the farnesylation of p21ras, the protein encoded for by the ras oncogene which is imnumber of human cancers. Farnesylation of p21ras is required for the plasma membrane localization anactivity of this protein. Our primary goal is to generate antisera that specifically recognize the fmoiety. Antibodies to prenylated cysteine (which are not currently available) will allow rapid detecproteins using standard procedures (e.g., SDS-PAGE, Western blotting, immunoprecipitation, ELISA). Tinclude (i) synthesize prenylated amino acid and peptide derivatives, (ii) couple prenylated derivatand (iii) immunize chickens and rabbits and screen sera for antibodies that recognize farnesylated aproteins.