17α-ethynylestradiol-3-glucuronide | 21343-43-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 17α-ethynylestradiol-3-glucuronide
• 英文别名: ethinylestradiol 3-glucuronide；D-Glucopyranosiduronic acid, (17I+/-)-17-hydroxy-19-norpregna-1,3,5(10)-trien-20-yn-3-yl；(2S,3S,4S,5R)-6-[[(8R,9S,13S,14S,17R)-17-ethynyl-17-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl]oxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
• CAS: 21343-43-1
• 化学式: C₂₆H₃₂O₈
• 分子量: 472.535
• InChiKey: DYBBEZHAELJFKW-RYOJVZDYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  137
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  uridine 5'-diphosphoglucuronic acid triammonium salt 、 炔雌醇 在 human UDP-glucuronosyltransferase1A₁₀ 、 magnesium chloride 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 生成 17α-ethynylestradiol-3-glucuronide
  参考文献：
  名称：

  Phenylalanine 93 of the human UGT1A10 plays a major role in the interactions of the enzyme with estrogens

  摘要：

  Little is currently known about the substrate binding site of the human UDP-glucuronosyltransferases (UGTs) and the structural elements that affect their complex substrate selectivity. In order to further understand and extend our earlier findings with phenylalanines 90 and 93 of UGT1A10, we have replaced each of them with Gly, Ala, Val, Leu, Ile or Tyr, and tested the activity of the resulting 12 mutants toward eight different substrates. Apart from scopoletin glucuronidation, the F90 mutants other than F90L were nearly inactive, while the F93 mutants' activity was strongly substrate dependent. Hence, F93L displayed high entacapone and 1-naphthol glucuronidation rates, whereas F93G, which was nearly inactive in entacapone glucuronidation, was highly active toward estradiol, estriol and even ethinylestradiol, a synthetic estrogen that is a poor substrate for the wild-type UGT1A10. Kinetic analyses of 4-nitrophenol, estradiol and ethinylestradiol glucuronidation by the mutants that catalyzed the respective reactions at considerable rates, revealed increased K-m, values for 4-nitrophenol and estradiol in all the mutants, whilst the K-m values of F93G and F93A for ethinylestradiol were lower than in control UGT1A10. Based on the activity results and a new molecular model of UGT1A10, it is suggested that both F90 and F93 are located in a surface helix at the far end of the substrate binding site. Nevertheless, only F93 directly affects the selectivity of UCT1A10 toward large and rigid estrogens, particularly those with substitutions at the D ring. The effects of F93 mutations on the glucuronidation of smaller or less rigid substrates are indirect, however. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2011.07.017