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Different Amino Acid Replacements in CAAX‐Tetrapeptide Based Peptidomimetic Farnesyltransferase Inhibitors
Author(s) -
Schlitzer Martin,
Sattler Isabel,
Dahse HansMartin
Publication year - 1999
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/(sici)1521-4184(19994)332:4<124::aid-ardp124>3.0.co;2-g
Subject(s) - farnesyltransferase , tetrapeptide , peptidomimetic , chemistry , stereochemistry , farnesyl diphosphate farnesyltransferase , amino acid , combinatorial chemistry , biochemistry , prenylation , enzyme , peptide
In a series of CAAX‐tetrapeptide based farnesyltransferase inhibitors it has been shown that the central AA‐dipeptide can be replaced by tranexamic acid, 4‐aminobenzenesulfonic acid, and 3‐amino‐N‐(2,3‐dimethylphenyl)benzenesulfonamide, respectively, yielding inhibitors active in the low micromolar range. Lipophilic derivatives of these compounds showed moderate antiproliferative activity against different tumor cell lines. A promising class of peptidomimetic farnesyltransferase inhibitors was discovered through the replacement of the terminal AAX motif of the CAAX‐tetrapeptide by 2‐acylamino‐5‐aminobenzophenones.