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Journal archive > 2010 > N 1 January-February

SPATIAL STRUCTURE OF THE СALIXARENE-AMINOPHOSPHONIC ACIDS
IS IMPORTANT FOR THEIR INHIBITION OF THE Na+,K+-АТРase ACTIVITY
IN PLASMATIC MEMBRANE OF SMOOTH MUSCLE CELLS

T. O. Veklich1, A. О. Shkrabak1, R. V. Rodik2, V. I. Boyko2, V. I. Kalchenko2, S. O. Kosterin1

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
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It was found that calixarene С-107 (5,17-diamino(2-pyridyl)methylphosphono-11,23-di-tret-butyl-26,28-dihydroxy-25,27-dipropoxycalix[4]arene) could effectively reduce Na+,K+-АТРase activity of the myometrium cell plasmatic membranes (the value of the apparent constant of inhibition I0.5 was 33 ± 4 nМ) while it practically did not influence the «basal» Mg2+-АТРase activity of the same membrane. In comparative experiments, we have shown that 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 activities of Na+,K+-АТРase and Mg2+-АТРаse over a wide range of concentrations. Hence, the influence of calixarene С-107 on Na+,K+-АТРase activity was caused by the joint action of two aminophosphonic substituents on the upper rim of the calixarene bowl. The isomer of calixarene С-107 – calixarene С-160 (5,11-diamino(2-pyridyl)methylphosphono-17,23-di-tret-butyl-26,28-dihydroxy-25,27-dipropoxycalix[4]arene) also did not influence the Na+,K+-АТРase and Mg2+-АТРаse activities of plasmatic membrane of myometrium cells. We carried out molecular modeling of calixarenes C-107 and C-160 and showed differences in interatomic distance between aminophosphonic substituents of mentioned calixarenes. We came to the conclusion that spatial structure of calixarene С-107, namely localization of two aminophosphonic substituents in 5,17 position of the upper rim of this calixarene, is crucial for inhibition of Na+,K+-АТРase activity. Using laser correlation spectroscopy it was found that the 100 µM solution of calixarene C-107 and 2.5% DMSO had microparticles with size range from 100 nm to 10 µm. Plasma membrane vesicles had average hydrodynamic diameter 401 ±?17?nm, but after interaction of these vesicles with calixarene C-107 we have registered the creation of some particles with sizes greater than 10 µm. Therefore membrane vesicles agglutinated to each other and/or to calixarene microparticles.

Key words: Na+,K+-ATPase, Mg2+-ATPase, plasma membrane, smooth muscle cells, myometrium, calixarenes, aminophosphonic acid, spatial structure, hydrodynamic dimensions.

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

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