Synthesis and evaluation of hydroxyproline-derived isoprenyltransferase inhibitors

Abstract A series of peptidomimetics based on a hydroxyproline scaffold was prepared and evaluated for inhibition of farnesyltransferase and geranylgeranyltransferase I in both enzymatic and cell-based assays. A number of analogs were potent and selective inhibitors of FTase, while one compound ( 22 ) was nonselective in the enzymatic assays but eight-fold selective for inhibition of GGTase in the cellular assay (IC 50 = 0.39 μM).