INHIBITORS OF FARNESYLTRANSFERASE AND RAS PROCESSING PEPTIDASE

Four analogs of the carboxy terminus of unprocessed p21(Ras) processin g protein were evaluated as inhibitors of the p21(Ras) farnesyltransfe rase and peptidase. While three showed no crossover of inhibitory acti vity between the enzymes, the fourth (a naphthyl-substituted peptide) inhibited both farnesyltransferase and peptidase, with IC(50)s of 16 m u M and 3 mu M, respectively. Such inhibition of more than one step of Ras processing may complicate assessment of the mode of action for so me inhibitors of Ras processing peptidase. (C) 1995 Academic Press, In c.