Synthesis and evaluation of some hydroxyproline-derived peptidomimetics as isoprenyltransferase inhibitors

CA1A2X peptidomimetics containing a modified proline at position A2 were prepared and evaluated for their ability to inhibit farnesyltransferase (FTase) and geranylgeranyltransferase I (GGTase I) in enzymatic and cell-based assays. These compounds inhibited farnesylation of H-ras in vitro in the high nanomolar to low micromolar IC50 range.