TY - JOUR
T1 - Synthesis and biological activity of semipeptoid farnesyltransferase inhibitors
AU - Reuveni, Hadas
AU - Gitler, Alex
AU - Poradosu, Enrique
AU - Gilon, Chaim
AU - Levitzki, Alexander
PY - 1997/1
Y1 - 1997/1
N2 - Semipeptoids derived from the Ras farnesyl transferase inhibitor, CVFM, were synthesized by the Simultaneous Multiple Analogue Peptide Synthesis methodology. The semipeptoids were screened for their in vitro inhibition potency towards farnesyl transferase and geranylgeranyl transferase. Structure-activity relationship studies led to a potent and selective inhibitor, HR-11, which blocks Ras farnesylation in vitro with an IC50 of 1.2 nM. The cell permeable methyl ester derivative of HR-11, HR-12, inhibits Ras farnesylation in intact cells with an IC50 of 10 μM and with no detectable inhibition of Rap1A/K-rev geranyl-geranylation.
AB - Semipeptoids derived from the Ras farnesyl transferase inhibitor, CVFM, were synthesized by the Simultaneous Multiple Analogue Peptide Synthesis methodology. The semipeptoids were screened for their in vitro inhibition potency towards farnesyl transferase and geranylgeranyl transferase. Structure-activity relationship studies led to a potent and selective inhibitor, HR-11, which blocks Ras farnesylation in vitro with an IC50 of 1.2 nM. The cell permeable methyl ester derivative of HR-11, HR-12, inhibits Ras farnesylation in intact cells with an IC50 of 10 μM and with no detectable inhibition of Rap1A/K-rev geranyl-geranylation.
UR - http://www.scopus.com/inward/record.url?scp=0031021479&partnerID=8YFLogxK
U2 - 10.1016/S0968-0896(96)00197-6
DO - 10.1016/S0968-0896(96)00197-6
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C2 - 9043660
AN - SCOPUS:0031021479
SN - 0968-0896
VL - 5
SP - 85
EP - 92
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 1
ER -
