(dPEG12)3-dPEG4-NHS

• 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: (dPEG12)3-dPEG4-NHS
• 英文别名: NHS-PEG4-(m-PEG12)3-ester；(2,5-dioxopyrrolidin-1-yl) 5-[2-[2-[2-[2-[3-[[1,3-bis[3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]-3-oxopropoxy]-2-[[3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]-3-oxopropoxy]methyl]propan-2-yl]amino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethylamino]-5-oxopentanoate
• 化学式: C₁₀₈H₂₀₆N₆O₅₂
• 分子量: 2420.83
• InChiKey: VOPFWBJWEJMWRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -10.7
• 重原子数：
  166
• 可旋转键数：
  145
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  606
• 氢给体数：
  5
• 氢受体数：
  52

反应信息

• 作为反应物：
  描述：

  (dPEG12)3-dPEG4-NHS 、 N-alpha-叔丁氧羰基-L-赖氨酸 以 二氯甲烷 为溶剂， 反应 72.0h， 以74%的产率得到Boc-Lys[(dPEG12)3-dPEG4]-OH
  参考文献：
  名称：

  Synthesis and Preliminary Biological Evaluation of High-Drug-Load Paclitaxel-Antibody Conjugates for Tumor-Targeted Chemotherapy

  摘要：

  The goal of this study was to design paclitaxel (PTX)-monoclonal antibody (mAb) prodrug conjugates (PTXMAbs) with the ability to deliver therapeutically significant doses of the drug to the tumor while avoiding the previously observed solubility limitations of conjugates with PTX:mAb molar ratios of > 3. New PTX conjugates were synthesized using the discrete poly(ethylene glycol) (dPEG) as linkers. These compounds, PTX-L-Lys[(dPEG12)(3)-dPEG4]-dPEG6-NHS (9a and 9b, for L = GL or SX, respectively), were then conjugated to the antiepidermal growth factor receptor mAb, C225 at increasing PTX:C225 ratios, producing completely soluble conjugates. Unlike the earlier PTXMAbs, buffered solutions of these conjugates remained homogeneous for extended periods of time. Fluorescence-activated cell sorting (FACS) analysis indicated preserved immunogenicity of the conjugates at all four substitution ratios, while cytotoxicity studies in MDA-MB-468 breast cancer cells indicated preservation of drug cytotoxicity. These conjugates may have potential in the development of high-drug-load tumor-targeting taxanes.

  DOI：

  10.1021/jm900899g