D-2-hydroxy-5-aminocaproic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: D-2-hydroxy-5-aminocaproic acid
• 英文别名: (R)-6-Amino-2-hydroxyhexanoic acid；(2R)-6-amino-2-hydroxyhexanoic acid
• 化学式: C₆H₁₃NO₃
• 分子量: 147.174
• InChiKey: CEWDTFLISAWJHG-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  10
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  83.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-氨基己酸 在 taurine dioxygenase F₂₀₆Y mutant 作用下， 以96%的产率得到
  参考文献：
  名称：

  牛磺酸双加氧酶催化羧酸的α-羟基氧化

  摘要：

  酶在合成有机化学中的应用范围仍然有限。为了扩展这一点，存在不同的策略，从酶的从头设计到通过转化不同的底物来利用已知酶的催化能力。表示为基质混杂。通过研究其在羧酸底物羟基化过程中的混杂催化特性，我们利用了来自大肠杆菌（E. coli）的牛磺酸双加氧酶（TauD）提供的合成潜力。TauD在羟化反应中显示出高选择性，但活性水平降低（26％转化率，> 96％ee）。通过在位置206（F206Y）处引入点突变，我们扩大了酶底物的范围，并改善了测试底物的转化率。与野生型酶相比，改良的催化剂的转化率至少提高了140％。酶变体接受的羧酸数量从四到八倍增加了一倍。

  DOI：

  10.1002/cctc.201501244

文献信息

• Highly stable biodegradable gene vector platforms for overcoming biological barriers
  申请人：The Johns Hopkins University

  公开号：US10335500B2

  公开（公告）日：2019-07-02

  A major challenge in non-viral gene delivery remains finding a safe and effective delivery system. Colloidally stable non-viral gene vector delivery systems capable of overcoming various biological barriers, are disclosed. The gene vectors are biodegradable, non-toxic and highly tailorable for use in specific applications. The vectors include a mixture of biodegradable copolymers, such as PBAE, and biodegradable polymers conjugated with hydrophilic, neutrally charged polymer, such as PEG. The gene vectors demonstrate broad vector distribution and high transgene delivery in vivo, providing an efficient non-viral gene delivery system for localized therapeutic gene transfer. Methods of using the vectors to overcome biological barriers including mucus gel and extracellular matrix are provided. Methods of formulating the vectors are also provided.

  非病毒基因递送的一个主要挑战仍然是找到一种安全有效的递送系统。本研究公开了胶体稳定的非病毒基因载体递送系统，该系统能够克服各种生物障碍。这些基因载体可生物降解、无毒，并可高度定制，以用于特定应用。这些载体包括可生物降解共聚物（如 PBAE）和与亲水性中性聚合物（如 PEG）共轭的可生物降解聚合物的混合物。这些基因载体在体内显示出广泛的载体分布和高转基因递送能力，为局部治疗基因转移提供了一种高效的非病毒基因递送系统。提供了使用载体克服生物屏障（包括粘液凝胶和细胞外基质）的方法。还提供了配制载体的方法。
• Engineering synthetic brain penetrating gene vectors
  申请人：The Johns Hopkins University

  公开号：US10695442B2

  公开（公告）日：2020-06-30

  A synthetic gene delivery platform with a dense surface coating of hydrophilic and neutrally charged PEG, capable of rapid diffusion and widespread distribution in brain tissue, and highly effective gene delivery to target cells therein has been developed. Nanoparticles including nucleic acids, are formed of a blend of biocompatible hydrophilic cationic polymers and they hydrophilic cationic polymer conjugated to hydrophilic neutrally charged polymers such as polyethylene glycol. The nanoparticles are coated with polyethylene glycol at a density that imparts a near neutral charge and optimizes rapid diffusion through the brain parenchyma. Methods of treating a disease or disorder of the brain including administering a therapeutically effective amount of nanoparticles densely coated with polyethylene glycol are also provided.

  现已开发出一种合成基因递送平台，其表面有一层亲水性和中性 PEG 的致密涂层，能够在脑组织中快速扩散和广泛分布，并能高效地向其中的靶细胞递送基因。包括核酸在内的纳米粒子由生物相容性亲水阳离子聚合物和亲水阳离子聚合物与亲水中性聚合物（如聚乙二醇）共轭的混合物组成。纳米粒子涂覆聚乙二醇的密度可赋予其接近中性的电荷，并优化其在脑实质中的快速扩散。还提供了治疗脑部疾病或失调的方法，包括施用治疗有效量的聚乙二醇致密包覆的纳米粒子。
• Particle formulation with polycation complex
  申请人：Yale University

  公开号：US10765638B2

  公开（公告）日：2020-09-08

  Compositions and methods for efficient delivery of therapeutic agents in vivo are provided. Typically, the compositions are in the form of polymeric particles formed from one or more therapeutic agent complexed with a polycationic polymer which is further encapsulated in one or more amphiphilic polymers, preferably diblock copolymer of a polyalkylene oxide and a polyester such as poly(D,L-lactide)-poly(ethylene glycol) (PLA-PEG). In the preferred embodiments, the chemotherapeutic agent reduces, or inhibits N-glycosylation of one or more receptor tyrosine kinases of cancer cells. Methods of using the particles to treat cancer are also provided.

  本文提供了在体内有效输送治疗剂的组合物和方法。典型的组合物是由一种或多种治疗剂与多阳离子聚合物络合而成的聚合物颗粒，该聚合物颗粒进一步封装在一种或多种两亲性聚合物中，最好是聚环氧烷和聚酯如聚（D,L-内酰胺）-聚乙二醇（PLA-PEG）的二嵌段共聚物。在优选的实施方案中，化疗剂可减少或抑制癌细胞中一种或多种受体酪氨酸激酶的 N-糖基化。还提供了使用颗粒治疗癌症的方法。
• ENGINEERING SYNTHETIC BRAIN PENETRATING GENE VECTORS
  申请人：The Johns Hopkins University

  公开号：EP3142704A1

  公开（公告）日：2017-03-22
• HIGHLY STABLE BIODEGRADABLE GENE VECTOR PLATFORMS FOR OVERCOMING BIOLOGICAL BARRIERS
  申请人：The Johns Hopkins University

  公开号：US20170072064A1

  公开（公告）日：2017-03-16

  A major challenge in non-viral gene delivery remains finding a safe and effective delivery system. Colloidally stable non-viral gene vector delivery systems capable of overcoming various biological barriers, are disclosed. The gene vectors are biodegradable, non-toxic and highly tailorable for use in specific applications. The vectors include a mixture of biodegradable copolymers, such as PBAE, and biodegradable polymers conjugated with hydrophilic, neutrally charged polymer, such as PEG. The gene vectors demonstrate broad vector distribution and high transgene delivery in vivo, providing an efficient non-viral gene delivery system for localized therapeutic gene transfer. Methods of using the vectors to overcome biological barriers including mucus gel and extracellular matrix are provided. Methods of formulating the vectors are also provided.