3- and 19-oximes of 16alpha,17alpha-cyclohexanoprogesterone derivatives: synthesis and interactions with progesterone receptor and other proteins.

Series of 3- and 19-oximes of 16alpha,17alpha-cyclohexanoprogesterone derivatives (pregna-d'-pentaranes) have been synthesized with the aim of probing the surfaces of progesterone receptor's and two other protein ligand binding pockets neighboring to 3- and 19-positions of steroid core. The same derivatives were also studied as possible intermediates for attachment to matrixes. The data on affinity constants suggest the presence of hydrophobic cavities with hydrophilic necks in the progesterone receptor and serum pentaranophylin near C19 of bound ligand and the lack of such a cavity in uterine pentaranophylin.

16alpha,17alpha-cycloalkane derivatives of progesterone intensively bind to a rat serum protein.

The interaction of 6alpha-methyl-[1,2-3H]16alpha,17alpha-cyclohexanoprogesterone with rat serum proteins has been studied. Specific binding of this ligand characterized by Kd = 0.36 +/- 0.

The size and/or configuration of the cycloalkane D' ring in pentacyclic progesterone derivatives are crucial for their high-affinity binding to a protein in addition to progesterone receptor in rat uterine cytosol.

[(3)H]labeled progesterone and a number of its 16alpha, 17alpha-cycloalkano derivatives with an additional three to six-membered D' ring were investigated for mutual competition and equilibrium binding to proteins from rat uterine cytosol. The interaction of all studied [(3)H]ligands with proteins was characterized by comparable affinity (K(d) in nM region) and apparent homogeneity in terms of affinity. At the same time, the concentrations of binding sites for ligands bearing 16alpha,17alpha cyclopentano, cyclohexano, or cyclohexeno substituents were several-fold higher than those for progesterone or 16alpha, 17alpha-cyclopropanoprogesterone.

Interactions of 16alpha,17alpha-cyclohexane derivatives of progesterone with the progesterone receptor from rat uterus.

Pregna-D'-pentaranes, 16alpha,17alpha-cyclohexanoprogesterone and 6alpha-methyl-16alpha,17alpha-cyclohexanoprogestero ne, were found to specifically interact with the progesterone receptor of soluble fraction from rat uterus. The formation of complexes between 3H-labeled derivatives of these steroids and the protein was complete within 1 to 3 h at 0-4 degreesC. The dissociation of these complexes was a two-phase process, the contribution of the fast dissociating complexes decreasing with increasing preincubation time.

Structural basis of steroid compounds interaction with "digitalis"-receptor sites of Na,K-dependent ATPase.

Twenty-two Steroid molecules have been tested for the inhibition Na,K-dependent ATPase at 10(-7)-10(-4) M concentrations. At the 10(-5) M concentration of the investigated molecules, inhibition ranged from 8 to 36%. To explain the structure-inhibition % relationship, we determined the value of heteropolarity or biphilicity moment of these molecules.