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

Authors :
El Oualid F
Burm BE
Leroy IM
Cohen LH
van Boom JH
van den Elst H
Overkleeft HS
van der Marel GA
Overhand M
Source :
Journal of medicinal chemistry [J Med Chem] 2004 Jul 29; Vol. 47 (16), pp. 3920-3.
Publication Year :
2004

Abstract

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, IC(50) = 250 +/- 20 nM). The methyl ester of 8 (13) selectively inhibited protein farnesylation in cultured cells.

Details

Language :
English
ISSN :
0022-2623
Volume :
47
Issue :
16
Database :
MEDLINE
Journal :
Journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
15267228
Full Text :
https://doi.org/10.1021/jm049927q