(2R,3R,4R,5R)-2,3,5,6-tetrahydroxy-N-(2-sulfanylethyl)-4-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhexanamide | 358388-21-3

• 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: (2R,3R,4R,5R)-2,3,5,6-tetrahydroxy-N-(2-sulfanylethyl)-4-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhexanamide
• CAS: 358388-21-3
• 化学式: C₁₄H₂₇NO₁₁S
• 分子量: 417.434
• InChiKey: VFWWUQIQKBGRRB-CRRXSQHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.9
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  210
• 氢给体数：
  10
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  半胱胺盐酸盐 、 乳糖酸 在 N-羟基丁二酰亚胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 、 1,4-dithio-D,L-threitol 作用下， 以 水 为溶剂， 反应 33.0h， 生成 (2R,3R,4R,5R)-2,3,5,6-tetrahydroxy-N-(2-sulfanylethyl)-4-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhexanamide
  参考文献：
  名称：

  Glyco-Nanoparticles with Sheddable Saccharide Shells: A Unique and Potent Platform for Hepatoma-Targeting Delivery of Anticancer Drugs

  摘要：

  Reduction-sensitive shell-sheddable glyco-nanoparticles were designed and developed based on poly(epsilon-caprolactone)-graft-SS-lactobionic acid (PCL-g-SS-LBA) copolymer for efficient hepatoma-targeting delivery of doxorubicin (DOX). PCL-g-SS-LBA was prepared by ring-opening copolymerization of epsilon-caprolactone and pyridyl disulfide carbonate followed by postpolymerization modification with thiolated lactobionic acid (LBA-SH) via thiol-disulfide exchange reaction. The dynamic light scattering (DLS) and transmission electron microscopy (TEM) showed that PCL-g-SS-LBA was self-assembled into monodisperse nanoparticles (SS-GNs) with a mean diameter of about 80 nm. SS-GNs while remaining stable under physiological conditions (37 degrees C, pH 7.4) were prone to rapid shell-shedding and aggregation in the presence of 10 mM dithiothreitol (DTT). DOX was loaded into SS-GNs with a decent loading content of 12.0 wt %. Notably, in vitro release studies revealed that about 80.3% DOX was released from DOX-loaded SS-GNs in 24 h under a reductive condition while low drug release (<21%) was observed for DOX-loaded PCL-g-LBA nanoparticles (reduction-insensitive control) under otherwise the same condition and for DOX-loaded SS-GNs under a nonreductive condition. The flow cytometry and confocal microscopy observations indicated that SS-GNs were efficiently taken up by asialoglycoprotein receptor (ASGP-R)-overexpressing HepG2 cells likely via a receptor-mediated endocytosis mechanism and DOX was released into the nuclei of cells following 4 h incubation. MTT assays showed that DOX-loaded SS-GNs exhibited a high antitumor activity toward HepG2 cells, which was comparable to free DOX and about 18-fold higher than their reduction-insensitive counterparts, while blank SS-GNs were nontoxic up to a tested concentration of 1.0 mg/mL. These shell-sheddable glyco-nanoparticles are promising for hepatoma-targeting chemotherapy.

  DOI：

  10.1021/bm401749t