Small Molecule Inhibitors of Histone Arginine Methyltransferases: Homology Modeling, Molecular Docking, Binding Mode Analysis, and Biological Evaluations

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• 作者：Rino Ragno ; Silvia Simeoni ; Sabrina Castellano ; Caterina Vicidomini ; Antonello Mai ; Antonella Caroli ; Anna Tramontano ; Claudia Bonaccini ; Patrick Trojer ; Ingo Bauer ; Gerald Brosch ; Gianluca Sbardella
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：March 22, 2007
• 年：2007
• 卷：50
• 期：6
• 页码：1241 - 1253
• 全文大小：855K
• 年卷期：v.50,no.6(March 22, 2007)
• ISSN：1520-4804

文摘

The screening of the inhibition capabilities of dye-like small molecules from a focused library against bothhuman PRMT1 and Aspergillus nidulans RmtA is reported as well as molecular modeling studies (homologymodeling, molecular docking, and 3-D QSAR) of the catalytic domain of the PRMT1 fungal homologueRmtA. The good correlation between computational and biological results makes RmtA a reliable tool forscreening arginine methyltransferase inhibitors. In addition, the binding mode analyses of tested derivativesreveal the crucial role of two regions, the pocket formed by Ile12, His13, Met16, and Thr49 and the SAMcisteinic binding site subsite. These regions should be taken into account in the design of novel PRMTinhibitors.