Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase

Cristiano Bolchi, Marco Pallavicini, Sergio K. Bernini, Giuseppe Chiodini, Alberto Corsini, Nicola Ferri, Laura Fumagalli, Valentina Straniero, Ermanno Valoti

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5408-5412
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number18
DOIs
Publication statusPublished - Sep 15 2011

Fingerprint

Peptidomimetics
Thiazoles
Prenylation
ras Proteins
Acids
Dipeptides
Acetic Acid
Smooth Muscle Myocytes
Cysteine
Muscle
Rats
Cells
imidazole
p21(ras) farnesyl-protein transferase
propionic acid
pyridine
2-aminothiazole

Keywords

  • Antiproliferative agents
  • Antitumors
  • Farnesyltransferase
  • Peptidomimetic inhibitors
  • Prenylation inihibitors

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Bolchi, C., Pallavicini, M., Bernini, S. K., Chiodini, G., Corsini, A., Ferri, N., ... Valoti, E. (2011). Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase. Bioorganic and Medicinal Chemistry Letters, 21(18), 5408-5412. https://doi.org/10.1016/j.bmcl.2011.07.003

Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase. / Bolchi, Cristiano; Pallavicini, Marco; Bernini, Sergio K.; Chiodini, Giuseppe; Corsini, Alberto; Ferri, Nicola; Fumagalli, Laura; Straniero, Valentina; Valoti, Ermanno.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 18, 15.09.2011, p. 5408-5412.

Research output: Contribution to journalArticle

Bolchi, C, Pallavicini, M, Bernini, SK, Chiodini, G, Corsini, A, Ferri, N, Fumagalli, L, Straniero, V & Valoti, E 2011, 'Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 18, pp. 5408-5412. https://doi.org/10.1016/j.bmcl.2011.07.003
Bolchi, Cristiano ; Pallavicini, Marco ; Bernini, Sergio K. ; Chiodini, Giuseppe ; Corsini, Alberto ; Ferri, Nicola ; Fumagalli, Laura ; Straniero, Valentina ; Valoti, Ermanno. / Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase. In: Bioorganic and Medicinal Chemistry Letters. 2011 ; Vol. 21, No. 18. pp. 5408-5412.
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