FARNESYL-DERIVED INHIBITORS OF RAS FARNESYL TRANSFERASE

The synthesis and evaluation of farnesyl-derived inhibitors of ras far nesyl transferase are presented. Evaluation of inhibitors of famesyl t ransferase and comparison with the previously described inhibitor was accomplished using purified enzyme and Amersham's Famesyl:Transferase enzyme assay kit. These results show an order of magnitude increase in inhibitory activity for beta-ketophosphonic acid over beta-hydroxypho sphonic acid. Incorporation of fluorines in alpha-position, led to an increase in inhibitory activity over the nonfluorinated analogues. (C) 1995 Academic Press. Inc.