P1-citronellyl P2-[2-acetamido-2-deoxy-α-D-galactopyranosyl] diphosphate | 1257984-08-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: P1-citronellyl P2-[2-acetamido-2-deoxy-α-D-galactopyranosyl] diphosphate
• 英文别名: [(2R,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl] [3,7-dimethyloct-6-enoxy(hydroxy)phosphoryl] hydrogen phosphate
• CAS: 1257984-08-9
• 化学式: C₁₈H₃₅NO₁₂P₂
• 分子量: 519.423
• InChiKey: WUTCUVVGIBLPJT-TVSHJMQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  33
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  201
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  P1-citronellyl P2-[2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-galactopyranosyl] diphosphate 在 sodium methylate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.5h， 以100%的产率得到P1-citronellyl P2-[2-acetamido-2-deoxy-α-D-galactopyranosyl] diphosphate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of carbohydrate-functionalized cyclodextrins and liposomes for hepatocyte-specific targeting

  摘要：

  针对糖结合受体的策略在细胞特异性药物和基因传递中具有吸引力。C型凝集素脱唾液酸糖蛋白受体（ASGPR）由于其仅由实质性肝细胞表达，特别适合于肝脏特异性传递。在本研究中，我们设计并开发了一种高效的碳水化合物功能化β-环糊精（βCDs）和脂质体的合成方法，用于肝细胞特异性传递。为了针对ASGPR进行靶向，罗丹明B负载的βCDs通过糖树枝状聚合物进行功能化。脂质体配备含有末端D-GalNAc残基的合成糖脂，以介导与ASGPR的结合。在人肝细胞癌细胞系HepG2中的摄取研究表明，显示末端D-Gal/D-GalNAc残基的βCDs和脂质体优先被内吞。相比之下，具有末端D-Man或D-GlcNAc残基的βCDs和脂质体的摄取明显减少。这里展示的D-Gal/D-GalNAc功能化的βCDs和脂质体实现了肝细胞特异性靶向。Gal功能化的βCDs是有效的分子载体，能够在体外将多柔比星传递到肝细胞并诱导凋亡。

  DOI：

  10.1039/c0ob00372g

文献信息

• Design, synthesis and biological evaluation of carbohydrate-functionalized cyclodextrins and liposomes for hepatocyte-specific targeting
  作者：Gonçalo J. L. Bernardes、Raghavendra Kikkeri、Maha Maglinao、Paola Laurino、Mayeul Collot、Sung You Hong、Bernd Lepenies、Peter H. Seeberger

  DOI：10.1039/c0ob00372g

  日期：——

  Targeting glycan-binding receptors is an attractive strategy for cell-specific drug and gene delivery. The C-type lectin asialoglycoprotein receptor (ASGPR) is particularly suitable for liver-specific delivery due to its exclusive expression by parenchymal hepatocytes. In this study, we designed and developed an efficient synthesis of carbohydrate-functionalized β-cyclodextrins (βCDs) and liposomes for hepatocyte-specific delivery. For targeting of ASGPR, rhodamine B-loaded βCDs were functionalized with glycodendrimers. Liposomes were equipped with synthetic glycolipids containing a terminal D-GalNAc residue to mediate binding to ASGPR. Uptake studies in the human hepatocellular carcinoma cell line HepG2 demonstrated that βCDs and liposomes displaying terminal D-Gal/D-GalNAc residues were preferentially endocytosed. In contrast, uptake of βCDs and liposomes with terminal D-Man or D-GlcNAc residues was markedly reduced. The D-Gal/D-GalNAc-functionalized βCDs and liposomes presented here enable hepatocyte-specific targeting. Gal-functionalized βCDs are efficient molecular carriers to deliver doxorubicin in vitro into hepatocytes and induce apoptosis.

  针对糖结合受体的策略在细胞特异性药物和基因传递中具有吸引力。C型凝集素脱唾液酸糖蛋白受体（ASGPR）由于其仅由实质性肝细胞表达，特别适合于肝脏特异性传递。在本研究中，我们设计并开发了一种高效的碳水化合物功能化β-环糊精（βCDs）和脂质体的合成方法，用于肝细胞特异性传递。为了针对ASGPR进行靶向，罗丹明B负载的βCDs通过糖树枝状聚合物进行功能化。脂质体配备含有末端D-GalNAc残基的合成糖脂，以介导与ASGPR的结合。在人肝细胞癌细胞系HepG2中的摄取研究表明，显示末端D-Gal/D-GalNAc残基的βCDs和脂质体优先被内吞。相比之下，具有末端D-Man或D-GlcNAc残基的βCDs和脂质体的摄取明显减少。这里展示的D-Gal/D-GalNAc功能化的βCDs和脂质体实现了肝细胞特异性靶向。Gal功能化的βCDs是有效的分子载体，能够在体外将多柔比星传递到肝细胞并诱导凋亡。