Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed replacing internal dipeptide AA with 4-amino-2-phenylbenzoic acid and cysteine (C) with 2-amino-4-thiazolyl-, 2-mercapto-4-thiazolyl-, 2-mercapto-4-imidazolyl- and 2-methylmercapto-4-thiazolyl-acetic or propionic acid. The compound in which C is replaced by 2-amino-4-thiazolylacetic acid inhibited FTase activity in the low nanomolar range and showed antiproliferative effect on rat aortic smooth muscle cells interfering with Ras farnesylation. On the basis of these results, 2-aminothiazole can be considered as an alternative to heterocycles, such as pyridine and imidazole, normally used in FTase inhibitors designed as non-thiol CAAX mimetics.
|Titolo:||Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase|
|Parole Chiave:||Antiproliferative agents; Antitumors; Farnesyltransferase; Peptidomimetic inhibitors; Prenylation inihibitors|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
Settore BIO/14 - Farmacologia
|Data di pubblicazione:||set-2011|
|Digital Object Identifier (DOI):||10.1016/j.bmcl.2011.07.003|
|Appare nelle tipologie:||01 - Articolo su periodico|