(2-吡啶基二硫代)-四聚乙二醇-醇 | 851961-99-4

• 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
• 中文名称: (2-吡啶基二硫代)-四聚乙二醇-醇
• 英文名称: 2-(2-(2-(2-(pyridin-2-yldisulfanyl)ethoxy)ethoxy)ethoxy)ethan-1-ol
• 英文别名: (2-pyridyldithio)-PEG4-alcohol；2-[2-[2-[2-(pyridin-2-yldisulfanyl)ethoxy]ethoxy]ethoxy]ethanol
• CAS: 851961-99-4
• 化学式: C₁₃H₂₁NO₄S₂
• 分子量: 319.446
• InChiKey: NVGYTXVKRZYCDH-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于DMSO、DCM、DMF

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2-吡啶基二硫代)-四聚乙二醇-醇 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-pyridyldithio)ethoxy]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：

  三缩四乙二醇 在 sodium methylate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 19.0h， 生成 (2-吡啶基二硫代)-四聚乙二醇-醇
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR INDUCING IMMUNE TOLERANCE
  [FR] COMPOSITIONS ET PROCÉDÉS D'INDUCTION D'UNE TOLÉRANCE IMMUNITAIRE

  摘要：

  本公开提供的一些实施例涉及承载期望产生耐受性的抗原的组成物，该抗原通过与靶向部分耦合、结合或以其他方式连接，该靶向部分配置为将组成物导向受试者的肝脏。在一些实施例中，通过聚合物连接剂将抗原与靶向部分连接。在一些实施例中，聚合物连接剂配置为在体内释放抗原。还提供了使用这些组成物来减少和/或预防对感兴趣抗原的未期望免疫反应的方法。

  公开号：

  WO2018232176A1

文献信息

• Compositions and methods for inducing immune tolerance
  申请人：The University of Chicago

  公开号：US11253579B2

  公开（公告）日：2022-02-22

  Several embodiments provided in the present disclosure relate to compositions that carry an antigen to which tolerance is desired, the antigen being coupled, bound, or otherwise joined to a targeting moiety, the targeting moiety configured to direct the composition to the liver of a subject. In several embodiments, the antigen in coupled to the targeting moiety by way of a polymeric linker. In several embodiments, the polymeric linker is configured to liberate the antigen in vivo. Methods of using the compositions to reduce and/or prevent unwanted immune responses against an antigen of interest are also provided.

  本公开提供的几个实施方案涉及携带抗原的组合物，抗原与靶向分子偶联、结合或以其他方式连接，靶向分子被配置为将组合物导向受试者的肝脏。在几个实施方案中，抗原通过聚合连接体与靶向分子连接。在几个实施方案中，聚合连接体被配置为在体内释放抗原。此外，还提供了使用组合物减少和/或预防针对相关抗原的不必要免疫反应的方法。
• GLYCOTARGETING THERAPEUTICS
  申请人：Ecole Polytechnique Fédérale de Lausanne

  公开号：EP3349784A1

  公开（公告）日：2018-07-25
• COMPOSITIONS AND METHODS FOR INDUCING IMMUNE TOLERANCE
  申请人：The University of Chicago

  公开号：US20220211826A1

  公开（公告）日：2022-07-07

  Several embodiments provided in the present disclosure relate to compositions that carry an antigen to which tolerance is desired, the antigen being coupled, bound, or otherwise joined to a targeting moiety, the targeting moiety configured to direct the composition to the liver of a subject. In several embodiments, the antigen in coupled to the targeting moiety by way of a polymeric linker. In several embodiments, the polymeric linker is configured to liberate the antigen in vivo. Methods of using the compositions to reduce and/or prevent unwanted immune responses against an antigen of interest are also provided.
• [EN] GLYCOTARGETING THERAPEUTICS<br/>[FR] AGENTS THÉRAPEUTIQUES DE GLYCOCIBLAGE
  申请人：ECOLE POLYTECHNIQUE FED LAUSANNE EPFL

  公开号：WO2017046652A1

  公开（公告）日：2017-03-23

  Several embodiments of the present disclosure relate to therapeutic compositions configured to target the liver of a subject and that are useful in the treatment or prevention of one or more of transplant rejection, autoimmune disease, food allergy, and immune response against a therapeutic agent. In several embodiments, the compositions are configured to target the liver and deliver antigens to which tolerance is desired. In several embodiments, the compositions are configured for clearance of a circulating protein or peptide or antibody associated with one or more of the above-mentioned maladies. Methods and uses of the compositions for induction of immune tolerance are also disclosed herein.
• [EN] COMPOUNDS FOR THE INDUCTION OF ANTIGEN-SPECIFIC IMMUNE TOLERANCE<br/>[FR] COMPOSÉS POUR L'INDUCTION D'UNE TOLÉRANCE IMMUNITAIRE SPÉCIFIQUE D'UN ANTIGÈNE
  申请人：ANOKION SA

  公开号：WO2021053589A1

  公开（公告）日：2021-03-25

  Disclosed are compounds for the induction of antigen-specific immune tolerance in a subject, the compounds comprising an antigen, a polymeric linker and a liver targeting moiety, wherein the polymeric linker comprises a terminal end unit lacking each of a dithioester and a dithiobenzoate and wherein the terminal end unit confers improved stability to the compound when in solution.