Approaches to the design of selective ligands for membrane progesterone receptor alpha

作者：Lisanova O V; Shchelkunova T A; Morozov I A; Rubtsov P M; Levina I S; Kulikova L E; Smirnov A N^*

来源：Biochemistry-Moscow, 2013, 78(3): 236-243.

DOI：10.1134/S0006297913030048

• membrane progesterone receptor alpha
• steroid ligand binding
• selectivity

A number of progesterone derivatives were assayed in terms of their affinity for recombinant human membrane progesterone receptor alpha (mPR alpha) in comparison with nuclear progesterone receptor (nPR). The 16 alpha,17 alpha-cycloalkane group diminished an affinity of steroids for mPR alpha without significant influence on affinity for nPR, thus rendering a prominent selectivity of ligands for nPR. On the contrary, substitution of methyl at C10 for ethyl or methoxy group moderately increased the affinity for mPR alpha and significantly lowered the affinity for nPR. A similar but even more prominent effect was observed upon substitution of the 3-oxo group for the 3-O-methoxyimino group. A significant preference towards mPR alpha was also rendered by the 17 alpha-hydroxy group and additional C6-C7-double bond. The data suggest that the modes of lig- and interaction with mPR alpha and nPR in the C3 region of the steroid molecule are different. One can speculate that combination of the above substitutions at C17, C10, C6, and C3 may give ligand(s) with high specificity towards mPR alpha over nPR. DOI: 10.1134/S0006297913030048

• 出版日期2013-3