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 language | English |
|---|---|
| Pages (from-to) | 5408-5412 |
| Number of pages | 5 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 21 |
| Issue number | 18 |
| DOIs | |
| Publication status | Published - Sep 15 2011 |
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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
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 journal › Article
}
TY - JOUR
T1 - Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase
AU - Bolchi, Cristiano
AU - Pallavicini, Marco
AU - Bernini, Sergio K.
AU - Chiodini, Giuseppe
AU - Corsini, Alberto
AU - Ferri, Nicola
AU - Fumagalli, Laura
AU - Straniero, Valentina
AU - Valoti, Ermanno
PY - 2011/9/15
Y1 - 2011/9/15
N2 - 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.
AB - 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.
KW - Antiproliferative agents
KW - Antitumors
KW - Farnesyltransferase
KW - Peptidomimetic inhibitors
KW - Prenylation inihibitors
UR - http://www.scopus.com/inward/record.url?scp=80051925890&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80051925890&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2011.07.003
DO - 10.1016/j.bmcl.2011.07.003
M3 - Article
C2 - 21802946
AN - SCOPUS:80051925890
VL - 21
SP - 5408
EP - 5412
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 18
ER -