化合物SHIELD-1 | 914805-33-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 中文名称: 化合物SHIELD-1
• 英文名称: (R)-3-(3,4-dimethoxyphenyl)-1-(3-(2-morpholinoethoxy)phenyl)propyl (S)-1-((S)-2-(3,4,5-trimethoxyphenyl)butanoyl)piperidine-2-carboxylate
• 英文别名: Shield-1；[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carboxylate
• CAS: 914805-33-7
• 化学式: C₄₂H₅₆N₂O₁₀
• 分子量: 748.914
• InChiKey: NMFHJNAPXOMSRX-PUPDPRJKSA-N

物化性质

• 熔点：
  54-55o C
• 沸点：
  837.6±65.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  54
• 可旋转键数：
  19
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  11

制备方法与用途

生物活性 Shield-1 是一种特异性、细胞可渗透且高亲和力的 FK506 结合蛋白-12 (FKBP) 配体，能够通过与突变的 FKBP (mtFKBP) 结合逆转其不稳定性，从而实现 mtFKBP 融合蛋白的条件表达。此外，Shield-1 还能稳定整个融合蛋白。

反应信息

• 作为产物：
  描述：

  六氢吡啶-alpha-羧酸 在 4-二甲氨基吡啶 、 碳酸氢钠 、 N,N'-二异丙基碳二亚胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 25.08h， 生成 化合物SHIELD-1
  参考文献：
  名称：

  廉价且可扩展的Shld合成

  摘要：

  报道了重要的FKBP配体Shld的合成。该合成避免了化学计量使用昂贵的手性试剂，保持了对映选择性，并提供了较高的总收率（39％）。该方法的主要特征是用于制备苯乙酸部分的对映选择性烷基化（结构单元A），用于获得手性二芳基-1-丙醇的催化对映选择性还原（结构单元C）以及对S-酒石酸酒石酸酯的直接酰化。而不是使用昂贵的Fmoc-哌酸。与以前的合成方法相比，构件A–C的组装过程是相反的，这也消除了对保护基团的需要。

  DOI：

  10.1021/acs.joc.8b00698

文献信息

• A CONDITIONAL REPLICATING CYTOMEGALOVIRUS AS A VACCINE FOR CMV
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP3251700A1

  公开（公告）日：2017-12-06

  The present invention relates to methods of inducing an immune response to cytomegalovirus (CMV) using a genetically modified CMV that is conditionally replication defective. The methods of the invention can be used to treat and/or prevent primary CMV infection, infection due to reactivation of a latent CMV and a super-infection of a different strain of CMV that had been previously encountered. The present invention also relates to a replication defective CMV which has been recombinantly altered to allow for external control of viral replication. Compositions comprising the replication defective CMV are also encompassed by the present invention.

  本发明涉及使用有条件复制缺陷的转基因 CMV 诱导巨细胞病毒（CMV）免疫反应的方法。本发明的方法可用于治疗和/或预防原发性巨细胞病毒感染、潜伏巨细胞病毒再活化引起的感染以及以前遇到过的不同株巨细胞病毒的超级感染。本发明还涉及一种有复制缺陷的 CMV，这种 CMV 经过重组改变，可以从外部控制病毒复制。本发明还包括含有复制缺陷 CMV 的组合物。
• Protein enriched microvesicles and methods of making and using the same
  申请人：Takara Bio USA, Inc.

  公开号：US10793828B2

  公开（公告）日：2020-10-06

  Protein enriched micro-vesicles and methods of making and using the same are provided. Aspects of the methods include maintaining a cell having a membrane-associated protein comprising a first dimerization domain and a target protein having a second dimerization domain under conditions sufficient to produce a micro-vesicle from the cell, wherein the micro-vesicle includes the target protein. Also provided are cells, reagents and kits that find use in making the micro-vesicles, as well as methods of using the micro-vesicles, e.g., in research and therapeutic applications.

  本文提供了富含蛋白质的微囊及其制造和使用方法。这些方法的各个方面包括在足以从细胞中产生微囊泡的条件下维持一个细胞，该细胞具有包含第一二聚化结构域的膜相关蛋白和具有第二二聚化结构域的目标蛋白，其中微囊泡包含目标蛋白。此外，还提供了可用于制造微囊的细胞、试剂和试剂盒，以及使用微囊的方法，例如在研究和治疗应用中。
• Chimeric antigen receptor (CAR) modulation
  申请人：TRUSTEES OF BOSTON UNIVERSITY

  公开号：US11059864B2

  公开（公告）日：2021-07-13

  The technology described herein is directed to CAR polypeptides and systems comprising repressible proteases. In combination with a specific protease inhibitor, the activity of said CAR polypeptides and systems and cells comprising them can be modulated. Also described herein are methods of using said CAR polypeptides and systems, for example to treat various diseases and disorders.

  本文所述技术针对的是包含可抑制蛋白酶的 CAR 多肽和系统。结合特定的蛋白酶抑制剂，可以调节所述 CAR 多肽和系统以及包含它们的细胞的活性。本文还描述了使用所述 CAR 多肽和系统的方法，例如用于治疗各种疾病和失调。
• CONDITIONAL REPLICATING CYTOMEGALOVIRUS AS A VACCINE FOR CMV
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US20140220062A1

  公开（公告）日：2014-08-07

  The present invention relates to methods of inducing an immune response to cytomegalovirus (CMV) using a genetically modified CMV that is conditionally replication defective. The methods of the invention can be used to treat and/or prevent primary CMV infection, infection due to reactivation of a latent CMV and a super-infection of a different strain of CMV that had been previously encountered. The present invention also relates to a replication defective CMV which has been recombinantly altered to allow for external control of viral replication. Compositions comprising the replication defective CMV are also encompassed by the present invention.
• PROTEIN ENRICHED MICROVESICLES AND METHODS OF MAKING AND USING THE SAME
  申请人：Clontech Laboratories, Inc.

  公开号：US20140364588A1

  公开（公告）日：2014-12-11

  Protein enriched micro-vesicles and methods of making and using the same are provided. Aspects of the methods include maintaining a cell having a membrane-associated protein comprising a first dimerization domain and a target protein having a second dimerization domain under conditions sufficient to produce a micro-vesicle from the cell, wherein the micro-vesicle includes the target protein. Also provided are cells, reagents and kits that find use in making the micro-vesicles, as well as methods of using the micro-vesicles, e.g., in research and therapeutic applications.