2-{2-[2-(2-{2-[2-(Pyridin-2-yldisulfanyl)-ethoxy]-ethoxy}-ethoxy)-ethoxy]-ethoxy}-ethanol | 851962-01-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-{2-[2-(2-{2-[2-(Pyridin-2-yldisulfanyl)-ethoxy]-ethoxy}-ethoxy)-ethoxy]-ethoxy}-ethanol
• 英文别名: 2-[2-[2-[2-[2-[2-(pyridin-2-yldisulfanyl)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol
• CAS: 851962-01-1
• 化学式: C₁₇H₂₉NO₆S₂
• 分子量: 407.552
• InChiKey: BPQVERMMCNRAIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  26.0
• 可旋转键数：
  19.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  79.27
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  2-{2-[2-(2-{2-[2-(Pyridin-2-yldisulfanyl)-ethoxy]-ethoxy}-ethoxy)-ethoxy]-ethoxy}-ethanol 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 2-[3,5-Dichloro-4-(2-{2-[2-(2-{2-[2-(pyridin-2-yldisulfanyl)-ethoxy]-ethoxy}-ethoxy)-ethoxy]-ethoxy}-ethoxy)-phenylamino]-benzoic acid
  参考文献：
  名称：

  Kinetic Stabilization of an Oligomeric Protein by a Single Ligand Binding Event

  摘要：

  Protein native state stabilization imposed by small molecule binding is an attractive strategy to prevent the misfolding and misassembly processes associated with amyloid diseases. Transthyretin (TTR) amyloidogenesis requires rate-limiting tetramer dissociation before misassembly of a partially denatured monomer ensues. Selective stabilization of the native TTR tetramer over the dissociative transition state by small molecule binding to both thyroxine binding sites raises the kinetic barrier of tetramer dissociation, preventing amyloidogenesis. Assessing the amyloidogenicity of a TTR tetramer having only one amyloidogenesis inhibitor (1) bound is challenging because the two small molecule binding constants are generally not distinct enough to allow for the exclusive formation of (TTRI)-I-. in solution to the exclusion of (TTRI2)-I-. and unliganded TTR. Herein, we report a method to tether one fibril formation inhibitor to TTR by disulfide bond formation. Occupancy of only one of the two thyroxine binding sites is sufficient to inhibit tetramer dissociation in 6.0 M urea and amyloidogenesis under acidic conditions by imposing kinetic stabilization on the entire tetramer. The sufficiency of single occupancy for stabilizing the native state of TTR provides the incentive to search for compounds displaying striking negative binding cooperativity (e.g., K-d1 in nanomolar range and K-d2 in the micromolar to millimolar range), enabling lower doses of inhibitor to be employed in the clinic, mitigating potential side effects.

  DOI：

  10.1021/ja042929f
• 作为产物：
  描述：

  六甘醇 在 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 sodium methylate 、 sodium hydride 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 2-{2-[2-(2-{2-[2-(Pyridin-2-yldisulfanyl)-ethoxy]-ethoxy}-ethoxy)-ethoxy]-ethoxy}-ethanol
  参考文献：
  名称：

  Kinetic Stabilization of an Oligomeric Protein by a Single Ligand Binding Event

  摘要：

  Protein native state stabilization imposed by small molecule binding is an attractive strategy to prevent the misfolding and misassembly processes associated with amyloid diseases. Transthyretin (TTR) amyloidogenesis requires rate-limiting tetramer dissociation before misassembly of a partially denatured monomer ensues. Selective stabilization of the native TTR tetramer over the dissociative transition state by small molecule binding to both thyroxine binding sites raises the kinetic barrier of tetramer dissociation, preventing amyloidogenesis. Assessing the amyloidogenicity of a TTR tetramer having only one amyloidogenesis inhibitor (1) bound is challenging because the two small molecule binding constants are generally not distinct enough to allow for the exclusive formation of (TTRI)-I-. in solution to the exclusion of (TTRI2)-I-. and unliganded TTR. Herein, we report a method to tether one fibril formation inhibitor to TTR by disulfide bond formation. Occupancy of only one of the two thyroxine binding sites is sufficient to inhibit tetramer dissociation in 6.0 M urea and amyloidogenesis under acidic conditions by imposing kinetic stabilization on the entire tetramer. The sufficiency of single occupancy for stabilizing the native state of TTR provides the incentive to search for compounds displaying striking negative binding cooperativity (e.g., K-d1 in nanomolar range and K-d2 in the micromolar to millimolar range), enabling lower doses of inhibitor to be employed in the clinic, mitigating potential side effects.

  DOI：

  10.1021/ja042929f

文献信息

• Reduction-Sensitive, Robust Vesicles with a Non-covalently Modifiable Surface as a Multifunctional Drug-Delivery Platform
  作者：Kyeng Min Park、Don-Wook Lee、Bijay Sarkar、Hyuntae Jung、Jeeyeon Kim、Young Ho Ko、Kyung Eun Lee、Hyesung Jeon、Kimoon Kim

  DOI：10.1002/smll.201000293

  日期：——

  facile internalization into targeted cells by receptor‐mediated endocytosis, and 4) efficient triggered release of entrapped drugs in a reducing environment such as cytoplasm. Furthermore, a significantly increased cytotoxicity of the anticancer drug doxorubicin to cancer cells is demonstrated using doxorubicin‐loaded SSCB[6]VC, the surface of which is decorated with functional moieties such as a folate–spermidine

  报道了一种新型的还原敏感性，健壮和生物相容性囊泡（SSCB [6] VC）的设计和合成，该囊泡由包含二硫键的两亲葫芦[6] uril（CB [6]）衍生物自组装而成。在六甘醇单元和CB [6]核之间。SSCB [6] VC的显着特征包括：1）使用异常强大的客体-客体化学作用，实现便捷，无损，无共价和模块化的表面修饰；2）高结构稳定性；3）通过受体介导的内吞作用容易地内化到靶细胞中，以及4）在还原性环境（例如细胞质）中有效触发包埋药物的释放。此外，载有阿霉素的SSCB [6] VC证明了抗癌药阿霉素对癌细胞的细胞毒性显着增加，其表面装饰有功能部分，例如叶酸-亚精胺结合物和异硫氰酸荧光素-亚精胺结合物作为靶向配体和荧光成像探针。具有这种独特功能的SSCB [6] VC可以用作靶向药物递送的多功能平台，这可能会在癌症治疗中找到有用的应用。这种基于超分子化学和CB [6]独特性质的新颖策略可以扩展