1,2-O-di-hexanoyl-sn-3-glycero-3-phosphothanolamine

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油磷脂
• 英文名称: 1,2-O-di-hexanoyl-sn-3-glycero-3-phosphothanolamine
• 英文别名: 1,2-dihexanoyl-sn-glycero-3-phosphoethanolamine；DHPE；2-azaniumylethyl (2R)-2,3-bis(hexanoyloxy)propyl phosphate；2-azaniumylethyl [(2R)-2,3-di(hexanoyloxy)propyl] phosphate
• 化学式: C₁₇H₃₄NO₈P
• 分子量: 411.433
• InChiKey: PELYUHWUVHDSSU-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  27
• 可旋转键数：
  19
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  、 1,2-O-di-hexanoyl-sn-3-glycero-3-phosphothanolamine 在 三乙胺 、 三氟乙酸五氟苯酯 作用下， 以 二氯甲烷 、 甲醇 、 氯仿 为溶剂， 反应 15.08h， 以31%的产率得到
  参考文献：
  名称：

  自噬蛋白LC3共轭物的半合成

  摘要：

  自噬是一种保守的分解代谢过程，涉及消除蛋白质，细胞器和病原体。自噬体形成是自噬的关键过程。与磷脂酰乙醇胺（PE）偶联的脂化Atg8 / LC3蛋白在自噬体生物发生中起关键作用。要了解Atg8 / LC3-PE在自噬小体形成和宿主-病原体相互作用中的功能，需要脂化Atg8 / LC3蛋白的制备和结构操纵。在本文中，我们报道了使用天然化学连接和氨解方法对具有不同PE片段或脂质修饰的LC3蛋白和突变体的半合成。

  DOI：

  10.1016/j.bmc.2017.05.051
• 作为产物：
  描述：

  己酸 在 palladium on activated charcoal 叔丁基过氧化氢 、 4-二甲氨基吡啶 、 氢气 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 15.25h， 生成 1,2-O-di-hexanoyl-sn-3-glycero-3-phosphothanolamine
  参考文献：
  名称：

  General Method for the Synthesis of Phospholipid Derivatives of 1,2-O-Diacyl-sn-Glycerols

  摘要：

  An efficient phosphite coupling protocol is described for the syntheses of the major classes of phospholipids that are derived from 1,2-O-diacyl-sn-glycerols and analogues thereof. The symmetrical diacyl glycerols 10c,d were prepared by straightforward acylation of 3-O-benzyl-sn-glycerol (7) with the appropriate carboxylic acid in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP). A simple method for preparing saturated and unstaturated mixed 1,2-O-diacyl-sn-glycerols was then devised that involved stepwise acylation of 7 with different alkyl carboxylic acids and debenzylation this procedure is exemplified by the preparation of 10a,b. The 1,2-O-diacyl-sn-glycerols 10a-d were then coupled with suitably protected lipid head groups employing reactive alkyl or aryl dichlorophosphites to give intermediate phosphite triesters in high overall yields. Oxidation or sulfurization of these phosphites proceeded smoothly to give the corresponding phosphate or phosphorothioate triesters, deprotection of which then provided the phosphatidylcholines 16 and 17, the phosphatidylethanolamine 20, the phosphatidylserine 28, and the phosphatidylinositols 37 and 38. Preparation of 37 and 38 required the invention of an improved method for resolving the isopropylidene-protected D-myo-inositol derivative 33. This phosphite coupling procedure was modified to assemble phospholipids bearing-polyunsaturated acyl side chains at the sn-2-position as exemplified by the preparation of the phosphatidylethanolamine 26. The one-pot phosphite coupling procedure is also applicable to the syntheses of a variety of other biologically interesting phospholipid analogues. For example, the phosphatidylinositol analogues 49-51, in which the hydroxyl group at C(2) of the inositol ring has been modified, were prepared in excellent overall yields by conjoining the 1,2-O-diacyl-sn-glycerol 10c with the protected inositol derivatives 44, 45, and 48. Phospholipid analogues that contain other replacements of the phosphate group including phosphoramidates and thiophosphates maybe prepared as evidenced by the syntheses of 56 and 61 in which the sn-3 oxygen atom of the 1,2-O-diacyl-sn-glycerol moiety is replaced with an N-benzyl group or a sulfur atom, respectively.

  DOI：

  10.1021/jo00096a023

文献信息

• Substrate Specificity in Short-Chain Phospholipid Analogs at the Active Site of Human Synovial Phospholipase A2
  作者：T. N. Wheeler、Steven G. Blanchard、Frank Fang、Yolanda Gray-Nunez、Cole O. Harris、Millard H. Lambert、Mukund M. Mehrotra、Derek J. Parks、R. C. Andrew

  DOI：10.1021/jm00050a009

  日期：1994.11

  The substrate specificity at the active site of recombinant human synovial fluid phospholipase A2 (hs-PLA2) was investigated by the preparation of a series of short-chain phospholipid analogs and measurement of their enzymatic hydrolysis at concentrations well below the critical micelle concentration. Substrates used in the study included 1,2-dihexanoylglycerophospholipids, 1,2-bis(alkanoylthio)glycerophospholipids

  通过制备一系列短链磷脂类似物并在远低于临界胶束浓度的条件下测量其酶解作用，研究了重组人滑液磷脂酶A2（hs-PLA2）活性位点的底物特异性。研究中使用的底物包括1,2-二己基甘油磷脂，1,2-双（烷酰基硫基）甘油磷脂和1-O-烷基-2-（烷酰基硫基）磷脂。仅观察到少量的1,2-二己酰基甘油磷脂脂质，且水解速率非常低，接近测定的检测极限。相反，选定的2-（烷酰硫基）-甘油磷脂在远低于其临界胶束浓度（cmc）的浓度下，被hs-PLA2水解得更高的速率。因此，1 2-双（己基硫基）甘油磷脂酰乙醇的ak（cat）/ K（M）= 1800 L mol-1 s-1。在计算的log P（cLogP）3-9范围内，具有直链sn-1和sn-2取代基的化合物的cLogP和log（k（cat）/ K（M）线性相关。 Sn-1醚和硫酯的水解速度相当，磷酸酯基团需要负电荷才能发挥酶的活性，sn-2取代基的不饱和度，芳香性和支链会大大减少周转率。
• FUSOGENIC PROPERTIES OF SAPOSIN C AND RELATED PROTEINS AND POLYPEPTIDES FOR APPLICATION TO TRANSMEMBRANE DRUG DELIVERY SYSTEMS
  申请人：Children's Hospital Medical Center

  公开号：EP3357490A1

  公开（公告）日：2018-08-08

  The present invention includes pharmaceutical and/or imaging agents and methods for delivering the agent(s) within and/or through the dermal, mucosal and other cellular membranes. The agents can include a fusogenic protein. This technology can be used for applications in which the objective is delivery of active agent within and/or beneath biological membranes and/or across the blood-brain barrier and neuronal membranes.

  本发明包括药物和/或成像制剂以及在皮肤、粘膜和其他细胞膜内和/或通过皮肤、粘膜和其他细胞膜输送制剂的方法。这些制剂可包括致熔蛋白。该技术可用于在生物膜内和/或生物膜下和/或穿过血脑屏障和神经元膜输送活性剂的应用。
• Liposomal formulation of nonglycosidic ceramides and uses thereof
  申请人：LUDWIG INSTITUTE FOR CANCER RESEARCH LTD.

  公开号：US10039715B2

  公开（公告）日：2018-08-07

  The invention provides liposomes containing nonglycosidic ceramides within their bilayers, and compositions thereof. These liposomes activate murine iNKT cells and induce dendritic cell (DC) maturation, both in vitro and in vivo at an efficacy that is comparable to their corresponding soluble nonglycosidic ceramides. Also provided are methods for treating diseases using the liposomes and compositions of the invention.

  本发明提供了在其双层内含有非糖苷类神经酰胺的脂质体及其组合物。这些脂质体可在体外和体内激活小鼠 iNKT 细胞并诱导树突状细胞（DC）成熟，其功效与相应的可溶性非糖苷神经酰胺相当。此外，还提供了使用本发明脂质体和组合物治疗疾病的方法。
• Combinations of mRNAs encoding immune modulating polypeptides and uses thereof
  申请人：ModernaTX, Inc.

  公开号：US10172808B2

  公开（公告）日：2019-01-08

  The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36γ (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).

  本公开涉及免疫调节多核苷酸（如mRNA）编码免疫应答引物多肽（如白细胞介素23（IL-23）多肽或白细胞介素36γ（IL-36-γ）多肽）和免疫应答共刺激信号多肽（如OX40L多肽）组合的制备、制造和治疗使用的组合物和方法。
• MRNA combination therapy for the treatment of cancer
  申请人：ModernaTX, Inc.

  公开号：US10335486B2

  公开（公告）日：2019-07-02

  The present disclosure relates to the use of nucleic acid (e.g., mRNA) combination therapies for the treatment of cancer. The disclosure provides compositions, and methods for their preparation, manufacture, and therapeutic use, wherein those compositions comprise at least two polynucleotides (e.g., mRNAs) in combination wherein the at least two polynucleotides are selected from the group consisting of (i) a polynucleotide encoding an immune response primer (e.g., IL23), (ii) a polynucleotide encoding an immune response co-stimulatory signal (e.g., OX40L), (iii) a polynucleotide encoding a checkpoint inhibitor (e.g., an anti CTLA-4 antibody), and, (iv) a combination thereof. The therapeutic methods disclosed herein comprise, e.g., the administration of a combination therapy disclosed herein for the treatment of cancer, e.g., by reducing the size of a tumor or inhibiting the growth of a tumor, in a subject in need thereof. In some aspects, the combination therapies disclosed herein disclosed are administered intratumorally.

  本公开涉及使用核酸（如mRNA）组合疗法治疗癌症。本公开提供了组合物及其制备、制造和治疗使用的方法，其中这些组合物包括至少两种组合在一起的多核苷酸（如mRNA），其中至少两种多核苷酸选自由以下组成的组(i)编码免疫应答引物的多核苷酸（如IL23），(ii)编码免疫应答引物的多核苷酸（如IL23），(iii)编码免疫应答引物的多核苷酸（如IL23），(iv)编码免疫应答引物的多核苷酸（如IL23）、IL23），(ii) 编码免疫应答共刺激信号（如 OX40L）的多核苷酸，(iii) 编码检查点抑制剂（如抗 CTLA-4 抗体）的多核苷酸，以及 (iv) 其组合。本文公开的治疗方法包括，例如，在有需要的受试者中施用本文公开的用于治疗癌症的组合疗法，例如，通过减小肿瘤大小或抑制肿瘤生长。在某些方面，本文公开的组合疗法是肿瘤内给药。