[Effect of mineralocorticoid analogs on Na(+),K(+)-dependent ATPase]. / Vliianie analogov mineralokortikoidov na Na(+),K(+)-zavisimuiu ATP-azu.

The effect of 42 steroids of the 20-ketopregnane series with heterocycles fused in positions 16 alpha and 17 alpha on the activity of Na+,K(+)-activated ATPase from pig kidney was studied. It was shown that the studied compounds could be divided into two groups. The compounds from the first group stimulate the ATPase at low concentrations (1 x 10(-8)-1 x 10(-7) M) and inhibit it at high concentrations (1 x 10(-4) M). The second group of compounds stimulated the sodium pump at either concentration. This is explained by the cooperative action of the ATPase tetramer: after the reaction of its first binding site with the ligand, the tetramer changes the conformation and specificity of its other binding sites. Computer analysis of this series of compounds was carried out and a mathematical model of the dependence of their activities on the structure of their substituents was obtained with a high correlation coefficient and a satisfactory predictive power. This confirmed the structural similarity of the studied compounds with respect to their interaction with the ATPase binding sites. The method of descriptor analysis that was applied in this study is a new variant of approximation; it is based on the use of symbol variables as descriptors.

The X-ray investigation of 16 alpha,17 alpha-thiazolidine derivatives of delta 4- and delta 5-pregnanes and conformational analysis of their oxathiolane analog.

An X-ray study of 3,20-dioxo-4-pregnene-[16 alpha,17 alpha-d]--2',2'-dimethylthiazolidine (I) and 3 beta-hydroxy-20-oxo-5--pregnene-[16 alpha,17 alpha-d]-2',2'- dimethylthiazolidine (II) has been carried out. Two independent molecules in crystal II have significantly different conformations of the D and E rings, although according to the atom-atom potential calculations the energy of interaction of these molecules with their neighbors in crystal is the same. The calculation of conformational energy of 3,20-dioxo-4-pregnene-[17 alpha,16 alpha-d]-2',2'--dimethyloxathiolane (III) by the molecular mechanics method (MMM) indicates a possibility of existence of two similar conformers also for this molecule. The MMM calculation shows also that the conformation of molecule III (as well as progesterone) with the 17 beta-acetyl group torsion angle C(16)C(17)C(20)0(20) close to -120 degrees is possible.