Novel reverse-turn mimics inhibit farnesyl transferase.
Reverse-turn inducing bicyclic lactams were incorporated into the substrate sequence recognized by farnesyl transferase to create inhibitors of RAS farnesylation. While the free peptides did not show any effect on the farnesylation, their Fmoc-protected counterparts impede the transformation of RAS with IC50's in the low micromolar range.
Liu
R
R
Cold Spring Harbor Laboratory, NY 11724, USA.
Dong
D L
DL
Sherlock
R
R
Nestler
H P
HP
Gennari
C
C
Mielgo
A
A
Scolastico
C
C
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D007700:Kinetics; D007769:Lactams / Q000138:chemical synthesis* / Q000378:metabolism*; D008956:Models, Chemical; D017433:Protein Structure, Secondary
D007769:Lactams; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase