Stereoselective interaction of an azole antifungal agent with its target, lanosterol 14 alpha-demethylase (cytochrome P-45014DM): a model study with stereoisomers of triadimenol and purified cytochrome P-45014DM from yeast.
Stereoselective interaction of an azole antifungal agent with its target, lanosterol 14 alpha-demethylase (cytochrome P-45014DM): a model study with stereoisomers of triadimenol and purified cytochrome P-45014DM from yeast.
复制标题
唑类抗真菌剂与其靶标羊毛甾醇 14 α-去甲基酶（细胞色素 P-45014DM）的立体选择性相互作用：三唑醇立体异构体和酵母纯化细胞色素 P-45014DM 的模型研究。
DOI：
10.1002/chir.530020103
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发表时间：
1990
期刊：
影响因子：
2
通讯作者：
Y. Aoyama
中科院分区：
文献类型：
--
作者：
Y. Yoshida;Y. Aoyama
研究了四种三唑醇立体异构体对纯化酵母羊毛甾醇 14 α-脱甲基酶（细胞色素 P-45014DM）（唑类抗真菌剂的主要靶标）的影响。 (1S,2R)-三唑醇是最有效的去甲基酶抑制剂，与酶的结合量低于 0.05 microM。该异构体还干扰细胞色素 P-45014DM 的化学还原以及 CO 与细胞色素的结合。其他异构体对该酶的抑制作用较低，活性顺序为（1R，2R）大于（1R，2S）大于或等于（1S，2S）。基于这些发现和报道的三唑醇立体异构体的优选构象（Anderson，N.H.等，Pestic.Sci.15：310-316，1984），预测疏水性叔丁基和对氯苯基相对于唑氮的取向对于将抗真菌剂适合于脱甲基酶的活性位点是重要的。
The effect of the four triadimenol stereoisomers on the purified yeast lanosterol 14 alpha-demethylase (cytochrome P-45014DM), the primary target of azole antifungal agents, was studied. (1S,2R)-Triadimenol was the most potent demethylase inhibitor and bound quantitatively to the enzyme below 0.05 microM. This isomer also interfered with the chemical reduction of cytochrome P-45014DM and the binding of CO to the cytochrome. The other isomers showed a lower inhibitory effect on the enzyme, and the order of activity was (1R,2R) greater than (1R,2S) greater than or equal to (1S,2S). Based on these findings and the reported preferred conformations for the triadimenol stereoisomers (Anderson, N.H. et al., Pestic. Sci. 15:310-316, 1984), it is predicted that orientation of the hydrophobic tert-butyl and p-chlorophenyl groups relative to the azole nitrogen is important to fit the antifungal agent in the active site of the demethylase.
酮康唑：大鼠肝脏中细胞色素 P-450 依赖性药物代谢的有效抑制剂。
DOI：
--
发表时间：
1984
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
--
作者：
Sheets,JJ;Mason,JI
通讯作者：
Mason,JI