Design, synthesis, and evaluation of sugar amino acid based inhibitors of protein prenyl transferases PFT and PGGT-1

被引：16
作者：
El Oualid, F
Burm, BEA
Leroy, IM
Cohen, LH
van Boom, JH
van den Elst, H
Overkleeft, HS
van der Marel, GA
Overhand, M
机构：
[1] Leiden Univ, Gorlaeus Labs, Leiden Inst Chem, NL-2300 RA Leiden, Netherlands
[2] TNO Prevent & Hlth, Gaubius Lab, NL-2301 CE Leiden, Netherlands
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 16期
关键词：
D O I：
10.1021/jm049927q
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Eleven analogues of the C-terminal Ca(1)a(2)X Motif found in natural substrates of the prenyl transferases PFT and PGGT-1 were synthesized and evaluated for their inhibition potency and selectivity against PFT and PGGT-1. Replacement of the central dipeptide part a(1)a(2) by a benzylated sugar amino acid resulted in a good and highly selective PFT inhibitor (8, IC50 = 250 +/- 20 nM). The methyl ester of 8 (13) selectively inhibited protein farnesylation in cultured cells.
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收藏
页码：3920 / 3923
页数：4
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