Application of oxime-diversification to optimize ligand interactions within a cryptic pocket of the polo-like kinase 1 polo-box domain.

@article{Zhao2016ApplicationOO,
  title={Application of oxime-diversification to optimize ligand interactions within a cryptic pocket of the polo-like kinase 1 polo-box domain.},
  author={Xue Zhi Zhao and David Hymel and Terrence R. Burke},
  journal={Bioorganic & medicinal chemistry letters},
  year={2016},
  volume={26 20},
  pages={
          5009-5012
        }
}
By a process involving initial screening of a set of 87 aldehydes using an oxime ligation-based strategy, we were able to achieve a several-fold affinity enhancement over one of the most potent previously known polo-like kinase 1 (Plk1) polo-box domain (PBD) binding inhibitors. This improved binding may result by accessing a newly identified auxiliary region proximal to a key hydrophobic cryptic pocket on the surface of the protein. Our findings could have general applicability to the design of… CONTINUE READING
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