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Journal archive > 2013 > N 2 March-April

THE СALIX[4]ARENE C-107 IS HIGHLY EFFECTIVE SUPRAMOLECULAR INHIBITOR
OF THE Na+,K+-АТРase OF PLASMATIC MEMBRANE

O. V. Bevza1, T. O. Veklich1, O. A. Shkrabak1, R. V. Rodik2, V. I. Kalchenko2, S. O. Kosterin1

 

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.;
2Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
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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 ?-? (stacking) interaction between calixarene and enzyme aminoacid residues, some of which are located near the active center of Na+,K+-АТРase, was discussed.

Key words: Na+,K+-ATPase, plasma membrane, smooth muscle cells, myometrium, calix[4]-arene C-107, computer simulation, docking.

The original article in Ukrainian is available for download in PDF format.

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