Hendry L B, Bransome E D, Lehner A F, Muldoon T G, Hutson M S, Mahesh V B
J Steroid Biochem. 1986 Apr;24(4):843-52. doi: 10.1016/0022-4731(86)90445-0.
Modeling studies revealed that progesterone, testosterone, and estradiol are stereochemically complementary to the cavity formed between base pairs in the DNA sequence, 5'-dTdG-3' X 5'-dCdA-3'. Each steroid aligned precisely with the topography of the cavity and formed 2 stereospecific hydrogen bonds linking phosphate oxygens on adjacent DNA strands. Hydrogen bonding donor-acceptor relationships were different for each hormone. The remarkable stereochemical specificity of the hormone-DNA complexes was demonstrated by the lack of complementarity of steroid enantiomers and steroid analogs having alternate ring systems and/or changes in the position of functional groups. Fit of molecules into DNA in the manner of the parent hormone correlated with biological activity. Antagonists also fit into the cavity but differed from agonists in their hydrogen bonding linkages to DNA and/or extended out of the cavity beyond the helix. Unlike flat intercalating agents which form stable complexes with DNA, wedge shaped steroids may thus be capable of forming reversible sequence-specific complexes with DNA. We conclude that the stereochemistry of DNA can be used to predict hormonal activity.
建模研究表明，孕酮、睾酮和雌二醇在立体化学上与DNA序列5'-dTdG-3'×5'-dCdA-3'中碱基对之间形成的空腔互补。每种甾体都与空腔的地形精确对齐，并形成2个立体特异性氢键，连接相邻DNA链上的磷酸氧。每种激素的氢键供体-受体关系都不同。甾体对映体和具有交替环系统和/或官能团位置变化的甾体类似物缺乏互补性，证明了激素-DNA复合物具有显著的立体化学特异性。分子以母体激素的方式与DNA的契合与生物活性相关。拮抗剂也能契合空腔，但在与DNA的氢键连接和/或延伸出螺旋外的空腔方面与激动剂不同。与能与DNA形成稳定复合物的平面嵌入剂不同，楔形甾体可能能够与DNA形成可逆的序列特异性复合物。我们得出结论，DNA的立体化学可用于预测激素活性。
