dexamethasone-21-thiopropionic acid | 166976-61-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: dexamethasone-21-thiopropionic acid
• 英文别名: 3-[[(11I(2),16I+/-)-9-Fluoro-11,17-dihydroxy-16-methyl-3,20-dioxopregna-1,4-dien-21-yl]thio]propanoic acid；3-[2-[(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl]sulfanylpropanoic acid
• CAS: 166976-61-0
• 化学式: C₂₅H₃₃FO₆S
• 分子量: 480.598
• InChiKey: AXTIEZAIJBMKGP-OCUNRLNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  dexamethasone-21-thiopropionic acid 、 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1-[3-[[6-(cyclohexylmethoxy)-7H-purin-2-yl]amino]phenyl]-1-deuterio-N-(3-phenylpropyl)methanesulfonamide
  参考文献：
  名称：

  Efficient Solid-Phase Synthesis of a Series of Cyclic and Linear Peptoid−Dexamethasone Conjugates for the Cell Permeability Studies

  摘要：

  Cyclic peptides and their cyclic analogs have received a great deal of attention because of their numerous interesting biological activities and their challenging chemical synthesis. It has also been hypothesized that they might improve the cell permeability compared to linear molecules by providing internal hydrogen bonding and generally decreasing the conformational flexibility. In this study, a series of cyclic and linear peptoid dexamethasone conjugates were rationally designed and efficiently synthesized on solid-phase for systematic cell permeability studies using reporter gene-based assays. These model compounds should be used to reveal how the cell permeability of cyclic molecules is affected by several physicochemical properties, especially, the reduced conformational flexibility and the ring size. In addition, the synthetic strategy that was adopted in this study can also provide a robust platform for postchemical modifications of various molecular scaffolds in solid-phase or solution-phase syntheses.

  DOI：

  10.1021/cc9001857
• 作为产物：
  描述：

  地塞米松 21-甲磺酸酯 、 3-巯基丙酸 在 三乙胺 作用下， 以 丙酮 为溶剂， 以95%的产率得到dexamethasone-21-thiopropionic acid
  参考文献：
  名称：

  [EN] METHODS FOR EFFICIENT DELIVERY OF THERAPEUTIC MOLECULES IN VITRO AND IN VIVO
  [FR] PROCÉDÉS D'ADMINISTRATION EFFICACE DE MOLÉCULES THÉRAPEUTIQUES IN VITRO ET IN VIVO

  摘要：

  本文描述了一种用于在哺乳动物内耳多种细胞类型中直接传递蛋白质的组合物。这些组合物可用于传递蛋白质（如基因编辑因子），以编辑与耳聋或相关疾病相关的遗传突变。传递基因组编辑蛋白质以编辑和纠正遗传突变，可保护或恢复遗传性耳聋的听力。治疗方法包括将这些分子进行胞内传递，以达到特定的治疗目标。

  公开号：

  WO2016069910A1

文献信息

• Quantitative Evaluation of the Relative Cell Permeability of Peptoids and Peptides
  作者：Yong-Uk Kwon、Thomas Kodadek

  DOI：10.1021/ja0668623

  日期：2007.2.1

  We evaluated quantitatively the relative cell permeability of peptides and peptides using a cell-based reporter gene-based assay. Generally, peptoids were much more cell permeable than the corresponding peptides, though the difference decreased with increasing length. These results suggest that peptoids may be useful reagents for manipulating the activities of intracellular proteins.
• Discovery and Characterization of a Peptide That Enhances Endosomal Escape of Delivered Proteins in Vitro and in Vivo
  作者：Margie Li、Yong Tao、Yilai Shu、Jonathan R. LaRochelle、Angela Steinauer、David Thompson、Alanna Schepartz、Zheng-Yi Chen、David R. Liu

  DOI：10.1021/jacs.5b05694

  日期：2015.11.11

  The inefficient delivery of proteins into mammalian cells remains a major barrier to realizing the therapeutic potential of many proteins. We and others have previously shown that superpositively charged proteins are efficiently endocytosed and can bring associated proteins and nucleic acids into cells. The vast majority of cargo delivered in this manner, however, remains in endosomes and does not reach the cytosol. In this study we designed and implemented a screen to discover peptides that enhance the endosomal escape of proteins fused to superpositively charged GFP (+36 GFP). From a screen of peptides previously reported to disrupt microbial membranes without known mammalian cell toxicity, we discovered a 13-residue peptide, aurein 1.2, that substantially increases cytosolic protein delivery by up to similar to 5-fold in a cytosolic fractionation assay in cultured cells. Four additional independent assays for nonendosomal protein delivery collectively suggest that aurein 1.2 enhances endosomal escape of associated endocytosed protein cargo. Structure function studies clarified peptide sequence and protein conjugation requirements for endosomal escape activity. When applied to the in vivo delivery of +36 GFP-Cre recombinase fusions into the inner ear of live mice, fusion with aurein 1.2 dramatically increased nonendosomal Cre recombinase delivery potency, resulting in up to 100% recombined inner hair cells and 96% recombined outer hair cells, compared to 0-4% recombined hair cells from +36-GFP-Cre without aurein 1.2. Collectively, these findings describe a genetically encodable, endosome escape-enhancing peptide that can substantially increase the cytoplasmic delivery of cationic proteins in vitro and in vivo.