2-(2-(2-(pyridin-2-yldisulfanyl)ethoxy)ethoxy)ethanol | 851961-98-3

• 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-(pyridin-2-yldisulfanyl)ethoxy)ethoxy)ethanol
• 英文别名: 2-(2-(2-(Pyridin-2-yldisulfanyl)ethoxy)ethoxy)ethan-1-ol；2-[2-[2-(pyridin-2-yldisulfanyl)ethoxy]ethoxy]ethanol
• CAS: 851961-98-3
• 化学式: C₁₁H₁₇NO₃S₂
• 分子量: 275.393
• InChiKey: JDYDXLWQXLYWTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(2-(2-(pyridin-2-yldisulfanyl)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-pyridyldithio)ethoxy]ethoxy]ethoxy]phenyl]amino]-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：

  三乙二醇 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-(pyridin-2-yldisulfanyl)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

• [EN] STABILIZATION OF BIOMOLECULES USING SUGAR POLYMERS<br/>[FR] STABILISATION DE BIOMOLÉCULES AU MOYEN DE POLYMÈRES DE GLUCIDES
  申请人：UNIV CALIFORNIA

  公开号：WO2013112897A1

  公开（公告）日：2013-08-01

  Compositions and methods for stabilizing biomolecules are disclosed. Specifically, the compositions include novel homopolymers or copolymers containing trehalose side chains conjugated to biomolecules. When such homopolymers or copolymers are placed in close proximity to biomolecules, such as proteins, the homopolymers or copolymers protect and/or stabilize the biomolecule. The compositions and methods may be suitable for use in various industries such as healthcare (pharmaceuticals), molecular biology, biofuels, paper, personal care, detergent, photographic, rubber, brewing, dairy and food processing industries.

  揭示了用于稳定生物分子的组合物和方法。具体来说，这些组合物包括含有与生物分子共轭的海藻糖侧链的新型同聚物或共聚物。当这种同聚物或共聚物与生物分子（如蛋白质）放置在紧密接触时，同聚物或共聚物可以保护和/或稳定生物分子。这些组合物和方法可能适用于各种行业，如医疗保健（制药）、分子生物学、生物燃料、纸张、个人护理、洗涤剂、摄影、橡胶、酿造、乳制品和食品加工行业。
• Trehalose Glycopolymers for Stabilization of Protein Conjugates to Environmental Stressors
  作者：Rock J. Mancini、Juneyoung Lee、Heather D. Maynard

  DOI：10.1021/ja2120234

  日期：2012.5.23

  times with lyophilization and 81% activity when the protein was heated at 90 °C for 1 h; this is in contrast to 16% and 18% retention of activity, respectively, for the wild-type protein alone. The glycopolymers were compared to equivalent concentrations of trehalose and poly(ethylene glycol) (PEG) and found to be superior at stabilizing the protein to lyophilization and heat. In addition, the protein-glycopolymer

  在此，我们报告了海藻糖侧链聚合物的合成，用于稳定蛋白质缀合物对环境压力的影响。糖单体 4,6-O-(4-乙烯基亚苄基)-α,α-海藻糖分两步以 40% 的产率合成，无需使用保护基化学。含有海藻糖侧基的聚合物是通过可逆加成-断裂链转移 (RAFT) 聚合反应制备的，使用两种不同的硫醇反应性链转移剂 (CTA)，随后通过二硫键与蛋白质结合。得到的糖聚合物是明确定义的，并且获得了从 4200 到 49 500 Da 的分子量范围。聚合物与硫醇化的鸡蛋清溶菌酶结合并纯化。相对于野生型蛋白质，当添加或共价连接到蛋白质时，糖聚合物显着增加了对冻干和热的稳定性。当溶菌酶冷冻干燥 10 次时，活性保持率高达 100%，当蛋白质在 90 °C 下加热 1 小时时，活性保持率为 81%；这与单独使用野生型蛋白质分别保留 16% 和 18% 的活性形成对比。将糖聚合物与等效浓度的海藻糖和聚（乙二醇）（PEG）进
• Stabilization of biomolecules using sugar polymers
  申请人：The Regents of the University of California

  公开号：US10543280B2

  公开（公告）日：2020-01-28

  Compositions and methods for stabilizing biomolecules are disclosed. Specifically, the compositions include novel homopolymers or copolymers containing trehalose side chains conjugated to biomolecules. When such homopolymers or copolymers are placed in close proximity to biomolecules, such as proteins, the homopolymers or copolymers protect and/or stabilize the biomolecule. The compositions and methods may be suitable for use in various industries such as healthcare (pharmaceuticals), molecular biology, biofuels, paper, personal care, detergent, photographic, rubber, brewing, dairy and food processing industries.

  本发明公开了用于稳定生物分子的组合物和方法。具体来说，这些组合物包括新型均聚物或共聚物，这些均聚物或共聚物含有与生物大分子共轭的三卤糖侧链。当这种均聚物或共聚物与蛋白质等生物大分子紧密接触时，均聚物或共聚物可保护和/或稳定生物大分子。这些组合物和方法可适用于各种行业，如医疗保健（制药）、分子生物学、生物燃料、造纸、个人护理、洗涤剂、照相、橡胶、酿造、乳品和食品加工行业。
• STABILIZATION OF BIOMOLECULES USING SUGAR POLYMERS
  申请人：The Regents of the University of California

  公开号：EP2807177B1

  公开（公告）日：2019-11-13
• US9901648B2
  申请人：——

  公开号：US9901648B2

  公开（公告）日：2018-02-27