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

• Main Authors: O. V. Bevza, T. O. Veklich, O. A. Shkrabak, R. V. Rodik, V. I. Kalchenko, S. O. Kosterin
• Format: Article
• Language: English
• Published: National Academy of Sciences of Ukraine and Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine. 2013-04-01
• Series: Ukrainian Biochemical Journal
• Subjects: calix[4]arene C-107; computer simulation; docking; myometrium; Na(+)-K(+)-ATPase; plasma membrane; smooth muscle cells
• Online Access: http://ukrbiochemjournal.org/wp-content/uploads/2015/10/Bevza_2_13.pdf

The inhibition of the Na+,K+-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 Na+,K+-АТРase activity more efficiently than ouabain did, while it did not practically influence the “basal” Mg2+-АТРase activity of the same membrane. The magnitude of the cofficient of inhibition I0.5 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 Na+,K+-АТРase and Mg2+-АТРаse. We carried out the computer simulation of interaction of calixarenes C-107 and the mentioned model compound with ligand binding sites of the Na+,K+-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 Na+,K+-АТРase, was discussed.