Trush V. Inhibition of protein tyrosine phosphatase 1B by phosphonate derivatives of calix[4]arenes

Calix[4]arene and thiacalix[4]arene phosphonic acid derivatives. Kinetic studies of protein tyrosine phosphatase 1B inhibition by calix[4]arene phosphonate derivatives. Evaluation of calix[4]arene phosphonic acids selectivity toward PTP1B in comparison with other human protein tyrosine phosphatases. Investigation of PTP1B inhibition mechanisms with macrocyclic compounds based on calix[4]arene platform. Elucidation of albumin-binding properties of thiacalix[4]arene phosphonic acid derivatives. The kinetic of enzymatic reactions, molecular docking studies, spectrophotometry and spectrofluorimetry. The new effective and selective PTP1B macrocyclic inhibitors with submicromolar inhibition constants were found. The one- and two-step mechanisms of complex formation of calix[4]arenes with PTP1B were described. The binding modes of macrocyclic inhibitors in the active site of PTP1B were characterized. For the first time the albumin-binding properties of thiacalix[4]arene phosphonic acids were shown. The results can be useful in the field of bioorganic chemistry.