Synthesis and evaluation of GGPP geometric isomers: Divergent substrate specificities of FTase and GGTase I

Authors
Zahn, TJ Whitney, J Weinbaum, C Gibbs, RA
Citation
Tj. Zahn et al., Synthesis and evaluation of GGPP geometric isomers: Divergent substrate specificities of FTase and GGTase I, BIOORG MED, 11(12), 2001, pp. 1605-1608
Citations number
22
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
12
Year of publication
2001
Pages
1605 - 1608
Database
ISI
SICI code
0960-894X(20010618)11:12<1605:SAEOGG>2.0.ZU;2-4
Abstract
A stereocontrolled synthetic route has been used to prepare two of the geom etric isomers of all-trans-GGPP. Neither of these isomers is effective subs trates for mammalian GGTase I, but 3 is a potent inhibitor of this enzyme ( IC50 = 100 nM). Surprisingly, both compounds are effective substrates for m ammalian FTase. (C) 2001 Elsevier Science Ltd. All rights reserved.