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.

Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase / C. Bolchi, M. Pallavicini, S.K. Bernini, G. Chiodini, A. Corsini, N. Ferri, L. Fumagalli, V. Straniero, E. Valoti. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 21:18(2011), pp. 5408-5412.

Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase

C. Bolchi;M. Pallavicini;G. Chiodini;A. Corsini;N. Ferri;L. Fumagalli;V. Straniero;E. Valoti
2011

Abstract

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.
Antiproliferative agents; Antitumors; Farnesyltransferase; Peptidomimetic inhibitors; Prenylation inihibitors
Settore CHIM/08 - Chimica Farmaceutica
Settore BIO/14 - Farmacologia
Article (author)
File in questo prodotto:
File Dimensione Formato  
Bioorganic & Medicinal Chemistry Letters 21 (2011) 5408–5412.pdf

non disponibili

Tipologia: Publisher's version/PDF
Dimensione 520.89 kB
Formato Adobe PDF
520.89 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/160699
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 17
social impact