Calixarene-based phosphinic acids as inhibitors of protein tyrosine phosphatases
Copyright policy )Calixarene-based phosphinic acids as inhibitors of protein tyrosine phosphatases
In the present work, the derivatives of calix[4]arene, thiacalix[4]arene, and sulfonylcalix[4]arene bearing four methylene(phenyl)phosphinic acid groups on the upper rim of the macrocycle were synthesized and studied as inhibitors of human protein tyrosine phosphatases. The inhibitory capacities of the three compounds towards PTP1B were higher than those for protein tyrosine phosphatases TC-PTP, MEG1, MEG2, and SHP2. The most potent sulfonylcalix[4]arene phosphinic acid displayed Ki value of 32 nM. The thiacalix[4]arene phosphinic acid was found to be a low micromolar inhibitor of PTP1B with selectivity over the other PTPs. The kinetic experiments showed that the inhibitors compete with the substrate for the active site of the enzyme. Molecular docking was performed to explain possible binding modes of the calixarene-based phosphinic inhibitors of PTP1B.
- National Academy of Sciences of Ukraine Ukraine
- University of California, San Diego United States
Molecular Docking Simulation, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Kinetics, Catalytic Domain, Humans, Calixarenes, Enzyme Inhibitors, Phosphinic Acids, Protein Binding
Molecular Docking Simulation, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Kinetics, Catalytic Domain, Humans, Calixarenes, Enzyme Inhibitors, Phosphinic Acids, Protein Binding
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