3- and 19-Oximes of 16α,17α-cyclohexanoprogesterone derivatives: Synthesis and interactions with progesterone receptor and other proteins
- 作者：Inna S. Levina ; Elena V. Pokrovskaya ; Lidya E. Kulikova ; Alexey V. Kamernitzky ; Vadim V. Kachala ; Alex ; er N. Smirnov
- 关键词：Oxime derivatives ; NMR spectroscopy ; Progesterone ; Progesterone receptor ; Binding affinity
- 刊名：Steroids
- 出版年：2008
- 期刊代码：142_0039128x
- 类别：bio
- 出版时间：September 2008
- 卷：73
- 期：8
- 页码：815-827
- 文件大小：621 K
摘要
Series of 3- and 19-oximes of 16
,17-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.
,17-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.