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. Any of 3-oxime substitutions were found to significantly diminish the ligand affinity for the progesterone receptor. It was also found that some of these modifications, in the Z-configuration particularly, might increase the affinity for serum and uterine pentaranophylins. The latter finding suggests the presence of large cavities near C3 of bound ligand in these proteins and interchangeability between 3-keto and 3-oxime groups in ligand-protein interactions.
Levina
Inna S
IS
Group of Chemistry of Steroids and Oxylipines, Zelinsky Institute of Organic Chemistry of Russian Academy of Sciences, Moscow, Russia.
Pokrovskaya
Elena V
EV
Kulikova
Lidya E
LE
Kamernitzky
Alexey V
AV
Kachala
Vadim V
VV
Smirnov
Alexander N
AN
D010091:Oximes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011980:Receptors, Progesterone / Q000187:drug effects* / Q000378:metabolism
D010091:Oximes; D011980:Receptors, Progesterone