Arginine methylation is a common post-translational modification that is crucial in modulating gene expression at multiple critical levels. The arginine methyltransferases (PRMTs) are envisaged as promising druggable targets, but their role in physiological and pathological pathways is far from being clear due to the limited number of modulators reported to date. In this effort, enzyme activators can be invaluable tools useful as gain-of-function reagents to interrogate the biological roles in cells and in vivo of PRMTs. Yet the identification of such molecules is rarely pursued. Herein we describe a series of aryl ureido acetamido indole carboxylates (dubbed "uracandolates"), able to increase the methylation of histone (H3) or nonhistone (polyadenylate-binding protein 1, PABP1) substrates induced by coactivator-associated arginine methyltransferase 1 (CARM1), both in in vitro and cellular settings. To the best of our knowledge, this is the first report of compounds acting as CARM1 activators.

Identification of Small-Molecule Enhancers of Arginine Methylation Catalyzed by Coactivator-Associated Arginine Methyltransferase 1 / Castellano, S.; Spannhoff, A.; Milite, C.; Dal Piaz, F.; Cheng, D.; Tosco, A.; Viviano, M.; Yamani, A.; Cianciulli, A.; Sala, M.; Cura, V.; Cavarelli, J.; Novellino, E.; Mai, Antonello; Bedford, M. T.; Sbardella, G.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 55:(2012), pp. 9875-9890. [10.1021/jm301097p]

Identification of Small-Molecule Enhancers of Arginine Methylation Catalyzed by Coactivator-Associated Arginine Methyltransferase 1.

MAI, Antonello;
2012

Abstract

Arginine methylation is a common post-translational modification that is crucial in modulating gene expression at multiple critical levels. The arginine methyltransferases (PRMTs) are envisaged as promising druggable targets, but their role in physiological and pathological pathways is far from being clear due to the limited number of modulators reported to date. In this effort, enzyme activators can be invaluable tools useful as gain-of-function reagents to interrogate the biological roles in cells and in vivo of PRMTs. Yet the identification of such molecules is rarely pursued. Herein we describe a series of aryl ureido acetamido indole carboxylates (dubbed "uracandolates"), able to increase the methylation of histone (H3) or nonhistone (polyadenylate-binding protein 1, PABP1) substrates induced by coactivator-associated arginine methyltransferase 1 (CARM1), both in in vitro and cellular settings. To the best of our knowledge, this is the first report of compounds acting as CARM1 activators.
2012
01 Pubblicazione su rivista::01a Articolo in rivista
Identification of Small-Molecule Enhancers of Arginine Methylation Catalyzed by Coactivator-Associated Arginine Methyltransferase 1 / Castellano, S.; Spannhoff, A.; Milite, C.; Dal Piaz, F.; Cheng, D.; Tosco, A.; Viviano, M.; Yamani, A.; Cianciulli, A.; Sala, M.; Cura, V.; Cavarelli, J.; Novellino, E.; Mai, Antonello; Bedford, M. T.; Sbardella, G.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 55:(2012), pp. 9875-9890. [10.1021/jm301097p]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/513465
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