Gly-OCho | 73670-26-5

• 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: Gly-OCho
• 英文别名: cholesterol aminoacetate；NH2-Gly-cholesterol；(8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-aminoacetate；cholesterol glycinate；3β-Aminoacetoxy-cholesten-(5)；3β-Glycyloxy-cholesten-(5)；O-glycyl-cholesterol；cholesteryl glycinate；CHG；Aminoessigsaeure-cholesterylester；O-Glycyl-cholesterin；Glycin-cholesterylester；[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] 2-aminoacetate
• CAS: 73670-26-5
• 化学式: C₂₉H₄₉NO₂
• 分子量: 443.714
• InChiKey: CJBSWQQUBIQQKU-OHPSOFBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Gly-OCho 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 149.0h， 生成 nicotinoyl-Pro-Pro-Gln-Leu-Pro-Gly-OCho
  参考文献：
  名称：

  Metabolism-Based Brain-Targeting System for a Thyrotropin-Releasing Hormone Analogue

  摘要：

  Gln-Leu-Pro-Gly, a progenitor sequence for the thyrotropin-releasing hormone (TRH) analogue [Leu(2)]TRH (pGlu-Leu-Pro-NH2), was covalently and bioreversibly modified on its N- and C-termini (by a 1,4-dihydrotrigonellyl and a cholesteryl group, respectively) to create lipoidal brain-targeting systems for the TRH analogue. The mechanism of targeting and the recovery of the parent peptide at the target site involve several enzymatic steps, including the oxidation of the 1,4-dihydropyridine moiety. Due to the lipid insolublity of the peptide pyridinium conjugate obtained after this reaction, one of the rudimentary steps of brain targeting (i.e., trapping in the central nervous system) can be accomplished. Our design also included spacer amino acid(s) inserted between the N-terminal residue of the progenitor sequence and the dihydrotrigonellyl group to facilitate the posttargeting removal of the attached modification. The release of the TRH analogue in the brain is orchestrated by a sequential metabolism utilizing esterase/lipase, peptidyl glycine alpha-amidating monooxygenase (PAM), peptidase cleavage, and glutaminyl cyclase. In addition to in vitro experiments to prove the designed mechanism of action, the efficacy of brain targeting for [Leu(2)]TRH administered in the form of chemical-targeting systems containing the embedded progenitor sequence was monitored by the antagonistic effect of the peptide on the barbiturate-induced anesthesia (measure of the activational effect on cholinergic neurons) in mice, and considerable improvement was achieved over the efficacy of the parent peptide upon casing this paradigm.

  DOI：

  10.1021/jm980526i
• 作为产物：
  描述：

  胆固醇 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 生成 Gly-OCho
  参考文献：
  名称：

  具有AIE效应的四苯乙烯二环四胆固醇的自组装和手性性质†

  摘要：

  固定的四苯基乙烯（TPE）螺旋桨状构象可用于发出强圆偏振发光（CPL）光，但必须解决该固定的螺旋桨状构象。由不需要拆分的手性基团诱导的TPE单元的单手螺旋构象也可以实现CPL发射，但是相关研究非常少见。本文合成了可以自组装成具有双分子层壳的纳米管的TPE二环四胆固醇，其荧光量子产率> 76％。由纳米管组成的薄膜显示出增强的第一正圆二向色性（CD）效果，并发出强的正CPL光。TPE二环四胆固醇在DCE中的悬浮液或溶液具有第一个负CD带和负CPL发射。相比之下，没有分子内环化作用的TPE四胆固醇自组装成非常柔软的“面条状”聚集体，并显示出非常弱的CD信号和CPL发射。TPE二环四胆固醇的CPL不对称因子大（≤3.0×10-3），是无循环的TPE四胆固醇的30倍。由于TPE二环四胆固醇CD光谱中的强双指带和聚集体中不存在螺旋结构，因此TPE二环四胆固醇的CD和CPL信号可归因于TPE单元普遍存在

  DOI：

  10.1039/c9tc02134e

文献信息

• Synthesis and gelation behaviors of five new dimeric cholesteryl derivatives
  作者：KaiQiang Liu、JunXia Peng、Min Xue、Ni Yan、Jing Liu、Yu Fang

  DOI：10.1007/s11426-010-4208-4

  日期：2011.3

  Five new diacid amides of di-cholesteryl l-glycinates were designed and prepared. The compounds with linkers containing 0, 1, 2, 3, or 4 methylene units are denoted as 1, 2, 3, 4, and 5, respectively. Their gelation behaviors in 25 solvents were tested as novel low-molecular-mass organic gelators (LMOGs). It was shown that the length of the linker connecting the two-cholesteryl residues in a gelator plays a crucial role in the gelation behavior of the compound. 1 gels 11 of the 25 solvents tested at a concentration lower than 1.0%, while 2 gels 17 of the solvents tested. 4 and 5, however, gel only 2 and 4 of them, respectively. SEM observation reveals that the lengths of the linkers and the identity of the solvents are the main factors affecting the structures of the aggregates in the gels. Experimentally, a clear linker effect on the microstructures of the gels was observed. As example, the aggregates of 1, 2 and 3 in benzene or 1-heptanol adopt structures of thin fibers, rods or lamellas, respectively. Furthermore, it was found that the gelation and aggregation behaviors of 2, 3, 4, and 5 in DMSO showed an even-odd effect.

  设计并制备了五种新型的二胆甾醇基L-甘氨酸盐二酸酰胺。这些具有0、1、2、3或4个亚甲基链节的连接基团的化合物分别被标记为1、2、3、4和5。它们作为新型低分子质量有机凝胶剂(LMOGs)在25种溶剂中的凝胶化行为被测试。结果表明，连接两个胆甾醇残基的连接链的长度对化合物的凝胶化行为起着至关重要的作用。在低于1.0%的浓度下，1凝胶化了25种测试溶剂中的11种，而2凝胶化了17种溶剂。然而，4和5分别仅凝胶化了2种和4种溶剂。扫描电镜观察揭示了连接链的长度和溶剂的性质是影响凝胶中聚集结构的主要因素。实验上，清晰地观察到了连接链对凝胶微观结构的影响。例如，1、2和3在苯或1-庚醇中的聚集物分别采用了细纤维、杆状或层状结构。此外，发现2、3、4和5在二甲基亚砜中的凝胶化和聚集行为呈现出偶-奇效应。
• Engineering liposomal nanoparticles of cholesterol-tethered amphiphilic Pt(<scp>iv</scp>) prodrugs with prolonged circulation time in blood
  作者：Payel Datta、Scott Bang、Zhizhou Yue、Travis Beach、Morgan Stilgenbauer、Han Wang、David J. Bowers、Manabu Kurokawa、Haihua Xiao、Yao-Rong Zheng

  DOI：10.1039/d0dt01297a

  日期：——

  widely used in the treatment of various solid tumors. However, a major challenge in the use of cisplatin and in the development of cisplatin derivatives, namely Pt(IV) prodrugs, is their premature reduction in the bloodstream before reaching cancer cells. To circumvent this problem, we designed liposomal nanoparticles coupled with a cholesterol-tethered amphiphilic Pt(IV) prodrug. The addition of cholesterol

  顺铂是一种铂基化学治疗剂，广泛用于治疗各种实体瘤。然而，在使用顺铂和开发顺铂衍生物即Pt（IV）前药方面的主要挑战是它们在到达癌细胞之前在血流中过早减少。为了解决这个问题，我们设计了脂质体纳米颗粒与胆固醇连接的两亲性Pt（IV）前药。胆固醇的添加起到稳定脂质体形成的作用，同时选择性地掺入胆固醇作为轴向配体也使Pt（IV）前药易于迁移到脂质体双层中。值得注意的是，Pt（IV）前药对人体血浆中的过早减少表现出明显的抗药性。在小鼠模型中的药代动力学分析还显示，纳米颗粒将Pt（IV）前药的半衰期显着延长至180分钟，与顺铂相比增加了6倍以上。重要的是，这种脂质修饰不会损害顺铂的遗传毒性，因为Pt（IV）前药可有效诱导卵巢癌细胞系中的DNA损伤和细胞凋亡。两者合计，我们的策略为如何稳定铂基化合物增加体内循环时间提供了新的见解，有望增强药物治疗的功效。
• Terthiophene Derivatives of Cholesterol-Based Molecular Gels and Their Sensing Applications
  作者：Chunmeng Yu、Min Xue、Ke Liu、Gang Wang、Yu Fang

  DOI：10.1021/la4046836

  日期：2014.2.11

  demonstrated that the film is photochemically unstable. Two hours UV irradiation of the film results in film 2, which is almost fluorescent silence. However, the presence of HAc vapor or the vapors of some other volatile organic liquids induces new fluorescence emission, laying the foundation for creating a turn-on type fluorescent sensor of the organic vapors. Furthermore, as a new type of low-molecular-mass

  设计并制备了三种新颖的胆固醇三苯并噻吩衍生物（TtGC，TtLPC，TtDPC），其中的两个结构单元分别通过甘氨酸，1-苯丙氨酸或d-苯丙氨酸的结构相连，它们的凝胶化行为在26液体进行了测试。结果表明，即使连接体的结构变化小，其化合物的凝胶化能力也不同。FTIR，11 H NMR和UV-vis测量表明，分子间氢键和范德华相互作用是凝胶形成的主要驱动力。对于TtDPC，CD和AFM测量表明它聚集为苯中左螺旋特征的手性结构。重要的是，可以通过改变胶凝剂浓度来微调凝胶网络的形态。考虑到荧光的亮度和凝胶网络独特的微观/纳米结构，通过将TtDPC /苯溶液（浸胶前）简单浸涂到玻璃板表面上就制成了荧光膜（膜1）。荧光研究表明该膜是光化学不稳定的。薄膜经过两个小时的紫外线照射后，形成了薄膜2，几乎是荧光无声的。然而，HAc蒸气或某些其他挥发性有机液体的蒸气的存在会引起新的荧光发射，从而为创建有机蒸气的开
• Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity
  作者：Chih-An Lin、Hui-Min Ho、Parthiban Venkatesan、Chiung-Yi Huang、Yu-Jhen Cheng、Yu-Hsing Lin、Hua-Yang Lin、Tzu-Yang Chen、Ming-Hsi Huang、Ping-Shan Lai

  DOI：10.3390/pharmaceutics13101569

  日期：——

  Clinical cases of allergic reaction that are due to excipients containing polyethylene glycol (PEG), a hydrophilic molecule commonly used in drug/vaccine formulations, has attracted much attention in recent years. In order to develop PEG-free adjuvants, we investigated the feasibility of natural ingredients in the human body such as hyaluronic acid in the form of hyaluronic acid-glycine cholesterol (HACH) conjugate as an excipient for vaccine formulation. Interestingly, HACH grafted with ~13 wt.% cholesterol has good water dispersity and can serve as an emulsifier to stabilize the squalene/water interfaces, yielding a milky white and isotropic emulsion (SQ@HACH) after being passed through a high-shear microfluidizer. Our results show that SQ@HACH particles possessed a unimodal average hydrodynamic diameter of approximately 190 nm measured by dynamic light scattering and exhibited good stability upon storage at 4 °C and 37 °C for over 20 weeks. The results of immunogenicity using a mouse model with ovalbumin (OVA) as the antigen revealed that SQ@HACH significantly enhanced antigen-specific immune responses, including the polarization of IgG antibodies, the cytokine secretions of T cells, and enhancement of cytotoxic T lymphocyte (CTL) activation. Moreover, SQ@HACH revealed lower local inflammation and rapidly absorbing properties compared with AlPO4 after intramuscular injection in vivo, indicating the potential functions of the HA-derived conjugate as an excipient in vaccine formulations for enhancement of T cell-mediated immunity.

  近年来，由于药物/疫苗配方中常用的亲水分子聚乙二醇（PEG）所含的辅料引起的过敏反应的临床病例备受关注。为了开发不含PEG的佐剂，我们研究了人体内天然成分如透明质酸的可行性，以透明质酸-甘氨酸胆固醇（HACH）共轭物作为疫苗配方的辅料。有趣的是，HACH嫁接了约13重量％的胆固醇具有良好的水分散性，并可作为乳化剂稳定角鲨烷/水界面，通过高剪切微流体器后形成乳白色和各向同性的乳液（SQ@HACH）。我们的结果表明，SQ@HACH颗粒具有单峰平均动态直径约为190纳米，经动态光散射测量，并在4℃和37℃下储存超过20周后表现出良好的稳定性。使用卵清蛋白（OVA）作为抗原的小鼠模型的免疫原性结果表明，SQ@HACH显着增强了特异性抗原免疫反应，包括IgG抗体的极化，T细胞的细胞因子分泌和细胞毒性T淋巴细胞（CTL）激活的增强。此外，与AlPO4相比，SQ@HACH在体内肌肉注射后表现出较低的局部炎症和快速吸收的特性，表明HA衍生的共轭物作为疫苗配方的辅料具有增强T细胞介导免疫的潜力。
• KITS FOR TOPICAL APPLICATION, REMOVAL, AND INACTIVATION OF THERAPEUTIC OR COSMETIC BOTULINUM TOXIN COMPOSITIONS
  申请人：ReVance Therapeutics, Inc.

  公开号：EP3248614A1

  公开（公告）日：2017-11-29

  This invention relates to methods and kits for safely removing and inactivating topical therapeutic or cosmetic compositions. The methods and kits according to the invention are particularly well suited for removing and inactivating highly toxic substances.

  本发明涉及安全去除和灭活局部治疗或化妆品组合物的方法和工具包。本发明的方法和试剂盒尤其适用于去除和灭活剧毒物质。