Identification of novel and selective non-peptide inhibitors targeting the polo-box domain of polo-like kinase 1 |
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Institution: | 1. Department of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC 27268, USA;2. Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA |
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Abstract: | A series of non-peptide inhibitors targeting the polo-box domain (PBD) of polo-like kinase 1 (Plk1) was designed based on the potent and selective minimal tripeptide Plk1 PBD inhibitor. Seven compounds were designed, synthesized and evaluated for fluorescence polarization (FP) assay. The most promising compound 10 bound to Plk1 PBD with IC50 of 3.37 μM and had no binding to Plk2 PBD or Plk3 PBD at 100 μM. Molecular docking study was performed and possible binding mode was proposed. MM/GBSA binding free energy calculation were in agreement with the observed experimental results. These novel non-peptide selective Plk1 PBD inhibitors provided new lead compounds for further optimization. |
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Keywords: | Polo like kinase 1 Polo-box domain Inhibitors Non-peptide Molecular docking |
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