The сalix[4]arene C-107 is highly effective supramolecular inhibitor of the Na+,K+-АТРase of plasmatic membrane

摘要

The inhibition of the Nasup+/sup,Ksup+/sup-АТРase activity of the myometrium cell plasma membranes with calixarene С-107 (5,17-diamino(2-pyridyl)methylphosphono-11,23-di-tret-butyl-26,28-dihydroxy-25,27-dipropoxycalix[4]arene) was investigated. It has been shown that calixarene С-107 reduced the Nasup+/sup,Ksup+/sup-АТРase activity more efficiently than ouabain did, while it did not practically influence the “basal” Mgsup2+/sup-АТРase activity of the same membrane. The magnitude of the cofficient of inhibition Isub0.5/sub was 33 ± 4 nМ, Hill coefficient was 0.38 ± 0.06. The model calixarene C-150 – the calixarene “scaffold” (26,28-dihydroxy-25,27-dipropoxycalix[4]arene), and the model compound М-3 (4-hydroxyaniline(2-pyridine)methylphosphonic acid) – a fragment of the calixarene С-107, had practically no influence on the enzymatic activity of Nasup+/sup,Ksup+/sup-АТРase and Mgsup2+/sup-АТРаse. We carried out the computer simulation of interaction of calixarenes C-107 and the mentioned model compound with ligand binding sites of the Nasup+/sup,Ksup+/sup-АТРase of plasma membrane and structure foundation of their intermolecular interaction was found out. The participation of hydrogen, hydrophobic, electrostatic and π-π (stacking) interaction between calixarene and enzyme aminoacid residues, some of which are located near the active center of Nasup+/sup,Ksup+/sup-АТРase, was discussed.