4-(2-carboxyethylthio)-11-deoxycortisol | 74997-25-4

• 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: 4-(2-carboxyethylthio)-11-deoxycortisol
• 英文别名: 3-[[(8R,9S,10R,13S,14S,17R)-17-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-4-yl]sulfanyl]propanoic acid
• CAS: 74997-25-4
• 化学式: C₂₄H₃₄O₆S
• 分子量: 450.596
• InChiKey: AZPRQKZZYTXAOS-KHDZLGLWSA-N

物化性质

• 沸点：
  671.1±55.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  111.9
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-羟基丁二酰亚胺 、 4-(2-carboxyethylthio)-11-deoxycortisol 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 4-(2-carboxyethylthio)-11-deoxycortisol N-succinimidyl ester
  参考文献：
  名称：

  An enzyme immunoassay system with a monoclonal antibody for the determination of 11-deoxycortisol.

  摘要：

  本研究描述了一种利用单克隆抗体测定 11-脱氧皮质醇的酶免疫测定方法。抗-11-脱氧皮质醇抗体是通过将分泌抗体的杂交瘤细胞接种到 BALB/c 小鼠腹水中产生的。用 N-琥珀酰亚胺酯法对 11-脱氧皮质醇进行酶标记。用β-半乳糖苷酶处理三种羧化类固醇的活化酯，得到酶标记抗原。在免疫测定中采用蛋白 A 双抗体法分离结合和游离部分。研究发现，单克隆抗体对由 4-（2-羧基乙硫基）-11-脱氧皮质醇制备的同源酶标记抗原具有很高的亲和力，而且这种结合会受到被分析物 11-脱氧皮质醇的抑制。在使用 11-脱氧皮质醇 3-（O-羧甲基）肟和 11-脱氧皮质醇 21-半琥珀酸酯制备的标签的异源系统中，分别观察到较低和无显著免疫反应性。这些结果表明，在制备免疫原时，单克隆抗体的抗原结合位点与 11-脱氧皮质醇部分互补，并覆盖了与载体连接位置较远的 11-脱氧皮质醇部分。同源检测系统显示出与使用氚作为示踪剂的放射免疫检测相当的高灵敏度和特异性。这些研究结果将有助于利用单克隆抗体开发各种免疫测定系统。

  DOI：

  10.1248/cpb.35.1497
• 作为产物：
  描述：

  11-deoxycortisol 21-tetrahydropyranyl ether 在 氢氧化钾 、 sodium hydroxide 、 双氧水 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 11.0h， 生成 4-(2-carboxyethylthio)-11-deoxycortisol
  参考文献：
  名称：

  Synthesis of corticosteroid haptens possessing the bridge at the C-4 position.

  摘要：

  为了获得用于放射免疫测定和酶免疫测定的特定抗血清，制备了新的氢化可的松、11-去氧氢化可的松和可的松的半抗原。通过使用适当保护的21-单叔丁基二甲基硅醚（即4-羟基类固醇的关键中间体）合成了4-羟基可的松和4-羟基-11-去氧可的松的4-半琥珀酸酯。另外，通过以巯基乙酸作为催化剂，催化开环4,5-环氧化物合成了类固醇的4-羧基-甲基硫衍生物。除此之外，相关半抗原的制备也进行了描述。

  DOI：

  10.1248/cpb.28.1294

文献信息

• Enzyme Labeling in Steroid Enzyme Immunoassays. Comparison of the p-Nitrophenyl Ester and N-Succinimidyl Ester Methods.
  作者：Hiroshi HOSODA、Katsuyuki FUKUDA、Yohko GOTOH

  DOI：10.1248/cpb.39.2373

  日期：——

  Enzyme labeling of steroids by the p-nitrophenyl ester method was investigated in comparison with the N-succinimidyl ester method. The active ester of a testosterone or 11-deoxycortisol derivative was treated with β-galactosidase and horseradish peroxidase to give labeled antigens. Various molar ratios of steroid to enzyme and pH conditions were tested. Satisfactory immunoreactivities with an anti-steroid antibody in each enzyme immunoassay system were obtained with the labeled antigens prepared at pH 8.5 by the use of molar ratios higher than 30. The enzyme labeling method should be useful in the case of polar steroids or drugs, since the p-nitrophenyl ester is relatively stable when compared with the N-succinimidyl ester.

  通过对硝基苯酯法与 N-琥珀酰亚胺酯法的比较，研究了类固醇的酶标记方法。睾酮或 11-脱氧皮质醇衍生物的活性酯经β-半乳糖苷酶和辣根过氧化物酶处理后可得到标记抗原。测试了类固醇与酶的各种摩尔比和 pH 条件。通过使用高于 30 的摩尔比，在 pH 值为 8.5 的条件下制备的标记抗原与抗类固醇抗体在每种酶免疫测定系统中都获得了令人满意的免疫反应性。这种酶标记方法适用于极性类固醇或药物，因为与 N-琥珀酰亚胺酯相比，对硝基苯酯相对稳定。
• Radioimmunoassay of 11-deoxycortisol. Specificity of antisera raised against 11-deoxycortisol-(C-4)-bovine serum albumin conjugates.
  作者：HIROSHI HOSODA、SHINICHI MIYAIRI、NORIHIRO KOBAYASHI、TOSHIO NAMBARA

  DOI：10.1248/cpb.30.2127

  日期：——

  In order to obtain specific antisera for use in immunoassays of 11-deoxycortisol, new hapten-carrier conjugates were prepared from 4-hemisuccinoyloxy-11-deoxycortisol, 4-(carboxymethylthio)-11-deoxycortisol, 4-(2-carboxyethylthio)-11-deoxycortisol and 4-(2-hemisuccinoyloxyethylthio)-11-deoxycortisol by coupling with bovine serum albumin employing the N-succinimidyl ester method. The specificity of anti-11-deoxycortisol antisera elicited in rabbits by immunization with these antigens was tested by crossreaction studies with closely related steroids and by measuring the amount of 11-deoxycortisol in plasma specimens by means of radioimmunoassay. The results showed that the antisera obtained were reasonably specific and useful for the determination of plasma 11-deoxycortisol levels in metyrapone tests. The assay can be done on methylene chloride extracts of plasma.

  为了获得用于 11-脱氧皮质醇免疫测定的特异性抗血清，我们用 4-半琥珀酰氧基-11-脱氧皮质醇、4-(羧基甲硫基)-11-脱氧皮质醇、4-(2-羧基乙硫基)-11-脱氧皮质醇和 4-(2-半琥珀酰氧基乙硫基)-11-脱氧皮质醇制备了新的单体-载体共轭物、4-(2-羧基乙硫基)-11-脱氧皮质醇和 4-(2-半琥珀酰氧基乙硫基)-11-脱氧皮质醇采用 N-琥珀酰亚胺酯法与牛血清白蛋白偶联。通过与密切相关的类固醇进行交叉反应研究，以及通过放射免疫测定法测量血浆标本中 11-脱氧皮质醇的含量，检验了用这些抗原免疫兔子所激发的抗 11-脱氧皮质醇抗血清的特异性。结果表明，获得的抗血清具有相当高的特异性，可用于在甲氧孕酮试验中测定血浆中 11-脱氧皮质醇的水平。该测定可在血浆的二氯甲烷提取物中进行。
• Effect of bridge heterologous combination on sensitivity in enzyme immunoassay for 11-deoxycortisol.
  作者：HIROSHI HOSODA、NORIHIRO KOBAYASHI、TOSHIO NAMBARA

  DOI：10.1248/cpb.31.953

  日期：——

  The effect of the bridge heterologous combination between antiserum and enzymelabeled steroid on sensitivity in heterogeneous enzyme immunoassay for 11-deoxycortisol has been investigated. Four 11-deoxycortisol derivatives possessing different bridges at C-4 were employed for the preparation of both antisera and enzyme-labeld antigens. They were 4-(carboxymethylthio)-11-deoxycortisol, 4-(2-carboxyethylthio)-11-deoxycortisol, 4-(2-hemisuccinoyloxyethylthio)-11-deoxycortisol, and 4-hemisuccinoyloxy-11-deoxycortisol. The N-succinimidyl esters of the carboxylated derivatives were reacted with β-galactosidase to give enzyme-labeled antigens. The antisera to 11-deoxycortisol used were those raised against the conjugates of these haptenic derivatives with bovine serum albumin. The sensitivities obtainable with four homologous and twelve heterologous systems were tested. When thioether derivatives were used for enzyme labeling, the effectiveness of heterology on assay sensitivity was dependent upon the length of the bridge. It was found that the heterologous system using the enzyme-labeled steroid obtained from a hapten having a bridge shorter than that used for antibody production resulted in an increase in sensitivity of the assay, whereas the use of a longer bridge was not effective. This finding is in good agreement with that obtained in our previous study on enzyme immunoassay for cortisol.

  抗血清和酶标记类固醇桥异构体组合对11-去氧皮质醇异质酶免疫分析灵敏度的影响已经过研究。四种在C-4处具有不同桥的11-去氧皮质醇衍生物被用于制备抗血清和酶标记抗原。它们分别是4-(羧甲基硫代)-11-去氧皮质醇、4-(2-羧乙基硫代)-11-去氧皮质醇、4-(2-半琥珀酰氧乙基硫代)-11-去氧皮质醇和4-半琥珀酰氧基-11-去氧皮质醇。羧基化衍生物的N-琥珀酰亚胺酯与β-半乳糖苷酶反应，生成酶标记抗原。11-去氧皮质醇抗血清是通过这些半抗原衍生物与牛血清白蛋白的共轭物产生的。四种同源和十二种异源系统的灵敏度进行了测试。当硫醚衍生物用于酶标记时，异源性对检测灵敏度的有效性取决于桥的长度。研究发现，异源系统使用从桥短于用于产生抗体的桥的半抗原获得的酶标记类固醇，可提高检测灵敏度，而使用更长的桥则无效。这一发现与我们之前对皮质醇酶免疫分析的研究结果非常一致