Kononets L. Sulfur-containing derivatives of phosphonic acids as inhibitors of phosphatases

New synthetic derivatives of phosphonic and methylenebisphosphonic acids as possible inhibitors of nonspecific alkaline phosphatases, nucleotide pyrophosphatase/phosphodiesterase 1 and some of protein tyrosine phosphatases. Purpose of the dissertation research has been to determine the influence laws of new sulfur-containing derivatives of phosphonic acids on activity of the alkaline phosphatases, nucleotide pyrophosphatase/phosphodiesterase 1 and some protein tyrosine phosphatases, and also studying of the mechanisms of action of the synthetic inhibitors in model systems. Spectrophotometric analysis, biochemical kinetics, molecular docking. For the first time properties of thioureidomethylenebisphosphonates as the inhibitors of bovine and human placenta alkaline phosphatases and also nucleotide pyrophosphatase/phosphodiesterase 1 from Bothrops atrox are established. Possibility of using the sulfur-containing macrocycles as a platform for design of the phosphonate inhibitors of the phosphatases is established. It was found, that phosphonis acids on a platform of calix[4]arenes are capable to effectively inhibit the protein tyrosine phosphatase from Yersinia and protein tyrosine phosphatase-b. The inhibitions of the alkaline phosphatases and the protein tyrosine phosphatases by the macrocyclic phosphonates were investigate with using of biochemical kinetics methods. The mechanisms of complexes formations of the phosphonate inhibitors with the enzymes are proved with help of molecular docking. Sphere of the use is bioorganic chemistry.