CALIX[4]ARENE C-99 INHIBITS MYOSIN ATPase ACTIVITY AND CHANGES THE ORGANIZATION OF CONTRACTILE FILAMENTS OF MYOMETRIUM.

Calix[4]arenes are cup-like macrocyclic (polyphenolic) compounds, they are regarded as promising molecular "platforms" for the design of new physiologically active compounds. We have earlier found that calix[4]arene C-99 inhibits the ATPase activity of actomyosin and myosin subfragment-1 of pig uterus in vitro. The aim of this study was to investigate the interaction of calix[4]arene C-99 with myosin from rat uterine myocytes.

[Protective effect of tiacalix[4]arene-tetrasulphonate on heavy metal inhibition of myometrium myosin subfragment-1 ATP-hydrolase activity].

Heavy metals have a negative effect on the contractility of uterine smooth muscles (myometrium), these effects can lead to various pathologies of a women reproductive system. To overcome these effects the methods for correcting the myometrium contractile activity are to be developed. Catalyzed by myosin ATPase ATP hydrolysis is the most important reaction in the molecular mechanism of myometrium contraction.

[Structural and functional bases of the intermolecular interaction of calix[4]arene C-97 with myosin subfragment-1 of myometrium].

Calix[4]arene C-97 (code is shown) is the macrocyclic compound which has lipophilic intramolecular higly-structured cavity formed by four aromatic cycles, one of which on the upper rim is modified by methylene bisphosphonic group. It was shown that calix[4]arene C-97 (100 microM) efficiently inhibits ATPase activity of myosin subfragment-1 from pig myometrium, the inhibition coefficient I(0.5) being 83 +/- 7 microM.

[Kinetic regularities and mechanisms of action of calix[4]arene C-99 on ATPase activity of myosin subfragment-1 of myometrium].

It has been shown that calix[4]arene C-99 inhibited myosin subfragment-1 ATPase of myometrium. This inhibition is noncompetitive as to ATP and Mg2+. At the same time, this compound reduces the seeming enzymatic hydrolysis maximum rate of nucleoside triphosphate with respect to ATP and Mg2+.

[Computer modeling of interaction of calix[4]arene C-99 with subfragment-1 of myometrium myosin].

In this work the computer design of interaction of calix[4]aren C-99 with a substrate-binding center of a functionally active area of a subfragment-1 myosin of the myometrium is carried out. It is shown when using methodology of molecular docking the receipt of ligand-receptor complexes which have geometry concerted with experimental data is possible. The cross-coupling of ATP and calix[4]aren C-99 on their orientation in ligand-binding center of subfragment-1 myosin of myometrium has been studied.