Identification and Characterization of New DNA G-Quadruplex Binders Selected by a Combination of Ligand and Structure-Based Virtual Screening Approaches

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• 作者：Stefano Alcaro ; Caterina Musetti ; Simona Distinto ; Margherita Casatti ; Giuseppe Zagotto ; Anna Artese ; Lucia Parrotta ; Federica Moraca ; Giosu猫 Costa ; Francesco Ortuso ; Elias Maccioni ; Claudia Sissi
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：February 14, 2013
• 年：2013
• 卷：56
• 期：3
• 页码：843-855
• 全文大小：654K
• 年卷期：v.56,no.3(February 14, 2013)
• ISSN：1520-4804

文摘

Nowadays, it has been demonstrated that DNA G-quadruplex arrangements are involved in cellular aging and cancer, thus boosting the discovery of selective binders for these DNA secondary structures. By taking advantage of available structural and biological information on these structures, we performed a high throughput in silico screening of commercially available molecules databases by merging ligand- and structure-based approaches by means of docking experiments. Compounds selected by the virtual screening procedure were then tested for their ability to interact with the human telomeric G-quadruplex folding by circular dichroism, fluorescence spectroscopy, and photodynamic techniques. Interestingly, our screening succeeded in retrieving a new promising scaffold for G-quadruplex binders characterized by a psoralen moiety.