Inhibitors of farnesyltransferase and Ras processing peptidase.
Four analogs of the carboxy terminus of unprocessed p21Ras protein were evaluated as inhibitors of the p21Ras processing farnesyltransferase and peptidase. While three showed no crossover of inhibitory activity between the enzymes, the fourth (a naphthyl-substituted peptide) inhibited both farnesyltransferase and peptidase, with IC50s of 16 microM and 3 microM, respectively. Such inhibition of more than one step of Ras processing may complicate assessment of the mode of action for some inhibitors of Ras processing peptidase.
Hall
C C
CC
Department of Oncology, Hoffmann-La Roche Inc., Nutley, NJ 07110-1199, USA.
Watkins
J D
JD
Ferguson
S B
SB
Foley
L H
LH
Georgopapadakou
N H
NH
D019883:Alkyl and Aryl Transferases; D000595:Amino Acid Sequence; D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014166:Transferases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D009842:Oligopeptides; D011480:Protease Inhibitors; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D016283:Proto-Oncogene Proteins p21(ras)