Structural Evidence of N6-Isopentenyladenosine As a New Ligand of Farnesyl Pyrophosphate Synthase

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• 作者：Mario Scrima ; Gianluigi Lauro ; Manuela Grimaldi ; Sara Di Marino ; Alessandra Tosco ; Paola Picardi ; Patrizia Gazzerro ; Raffaele Riccio ; Ettore Novellino ; Maurizio Bifulco ; Giuseppe Bifulco ; Anna Maria D鈥橴rsi
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：September 25, 2014
• 年：2014
• 卷：57
• 期：18
• 页码：7798-7803
• 全文大小：291K
• ISSN：1520-4804

文摘

N6-isopentenyladenosine (i6A), a modified nucleoside belonging to the cytokinin family, has shown in humans many biological actions, including antitumoral effects through the modulation of the farnesyl pyrophosphate synthase (FPPS) activity. To investigate the relationship between i6A and FPPS, we undertook an inverse virtual screening computational target searching, testing i6A on a large panel of 3D protein structures involved in cancer processes. Experimentally, we performed an NMR investigation of i6A in the presence of FPPS protein. Both inverse virtual screening and saturation transfer difference (STD) NMR outcomes provided evidence of the structural interaction between i6A and FPPS, pointing to i6A as a valuable lead compound in the search of new ligands endowed with antitumoral potential and targeting FPPS protein.