CONSTRAINED ANALOGS OF KCVFM WITH IMPROVED INHIBITORY PROPERTIES AGAINST FARNESYL TRANSFERASE

被引:34
作者
CLERC, FF
GUITTON, JD
FROMAGE, N
LELIEVRE, Y
DUCHESNE, M
TOCQUE, B
JAMESSURCOUF, E
COMMERCON, A
BECQUART, J
机构
[1] Rhône-Poulenc Rorer S.A.- Centre de Recherches de Vitry-Alfortville 13, 94403 Vitry-sur-Seine
关键词
D O I
10.1016/0960-894X(95)00314-J
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Constrained analogs of KCVFM, reported thus far as one of the most active peptidic inhibitors of farnesyl transferase, have been synthesized. Replacement of Val-Phe with Val-Tic and (N-Me)Val-Tic led to dramatically more active analogs possessing favored extended conformations. Based on molecular modelling studies the design and synthesis of various conformational probes to be substituted for Val and Phe led to a good correlation between the ratio of extended conformers and biological activity.
引用
收藏
页码:1779 / 1784
页数:6
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