Identification of protein-protein interfacial interactions in cancer has greater advantage for developing small molecule drugs as therapeutics. Currently, the drug screening methods are expensive, and the resulting high cost of anticancer drugs poses a serious concern for most patients to afford. Therefore, developing rapid, inexpensive methods are valuable. We show that electro-chemical drug screening methods can offer remarkable simplicity, high sensitivity, and ease of transforming into high-throughput format in a relatively inexpensive manner, which are advantageous for use in drug development, as a complementary method. The interaction between p53-MDM2 is selected as a model-system to develop our electrochemical drug screening method. p53 is a tumor suppressor protein and MDM2 functions as a negative regulator of p53 function.Therefore the accumulation of MDM2 hinders the tumor-suppression activity of p53.Our approach is to construct a thin film assembly of p53-MDM2 on electrode surface with one of the proteins incorporated with an electrochemical tag, for detection purpose. The dissociation of the two proteins by a nutlin type small molecule drug leads to the diminished amount of electrochemically active species on the electrode surface, and the associated signal decrease. Preliminary experimental evidence reveals that the signal changes correspond  only to the electro-active tag in the assembly, and the signal intensity correlated inversely with increase in drug concentration. Further optimization of this method and experiments on label-free electrochemical methodology will be discussed.Financial support by the Oklahoma State University is greatly acknowledged.

Electrochemical drug screening for targeted protein: Protein interfaces in cancer

247th National Meeting (2014)

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