N-biotinyl-N′-(3-(4-phenylthiocarbonylthio-4-cyanovaleryl)-3,6-dioxaoctane-1,8-diamine) | 1212057-35-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: N-biotinyl-N′-(3-(4-phenylthiocarbonylthio-4-cyanovaleryl)-3,6-dioxaoctane-1,8-diamine)
• 英文别名: [5-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethylamino]-2-cyano-5-oxopentan-2-yl] benzenecarbodithioate
• CAS: 1212057-35-6
• 化学式: C₂₉H₄₁N₅O₅S₃
• 分子量: 635.873
• InChiKey: KWKYXQDKOWXXKQ-ZALQVQBLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  42
• 可旋转键数：
  20
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  224
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4,4'-偶氮双(4-氰基戊酸) 在 2,6-二甲基吡啶 、 三氟乙酸酐 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 44.0h， 生成 N-biotinyl-N′-(3-(4-phenylthiocarbonylthio-4-cyanovaleryl)-3,6-dioxaoctane-1,8-diamine)
  参考文献：
  名称：

  Biotinylated Polyacrylamide-Based Metal-Chelating Polymers and Their Influence on Antigen Recognition Following Conjugation to a Trastuzumab Fab Fragment

  摘要：

  We report the synthesis and characterization of metal-chelating polymers (MCPs) with a terminal biotin and a polyacrylamide backbone harboring multiple diethylenetriaminepentaacetic acid (DTPA) chelating sites. These polymers are conjugated to a streptavidin (SAv)-modified Fab fragment of trastuzumab (tmFab) and subsequently complexed with In-111 through DTPA. Trastuzumab has specific targeting ability toward human epidermal growth factor receptor-2 (HER2), which is overexpressed on some types of breast cancer cells and ovarian cancer cells. In-111 can generate Auger electrons which cause lethal DNA double strand breaks. The radioimmunoconjugates (RICs) were designed to target HER2 overexpressing cancer cells and carry multiple copies of In-111 to these cells. The mole maximum specific activities of these polymers were investigated by loading the polymers with In-111 at an increasing In-111 to polymer ratio. The polymers show 55-fold to 138-fold higher maximum specific activity than DTPA modified tmFab-SAv. Moreover, the HER2 immunoreactivities of these RICs were evaluated by measuring their specific binding ability toward HER2 overexpressing SKOV-3 ovarian cancer cells. The results demonstrate that although in the presence of polymer there is increased nonspecific binding, HER2 targeting ability was retained, ensuring the radionuclide delivery ability of these RICs.

  DOI：

  10.1021/bm300843u

文献信息

• Biotinylated Polyacrylamide-Based Metal-Chelating Polymers and Their Influence on Antigen Recognition Following Conjugation to a Trastuzumab Fab Fragment
  作者：Peng Liu、Amanda J. Boyle、Yijie Lu、Raymond M. Reilly、Mitchell A. Winnik

  DOI：10.1021/bm300843u

  日期：2012.9.10

  We report the synthesis and characterization of metal-chelating polymers (MCPs) with a terminal biotin and a polyacrylamide backbone harboring multiple diethylenetriaminepentaacetic acid (DTPA) chelating sites. These polymers are conjugated to a streptavidin (SAv)-modified Fab fragment of trastuzumab (tmFab) and subsequently complexed with In-111 through DTPA. Trastuzumab has specific targeting ability toward human epidermal growth factor receptor-2 (HER2), which is overexpressed on some types of breast cancer cells and ovarian cancer cells. In-111 can generate Auger electrons which cause lethal DNA double strand breaks. The radioimmunoconjugates (RICs) were designed to target HER2 overexpressing cancer cells and carry multiple copies of In-111 to these cells. The mole maximum specific activities of these polymers were investigated by loading the polymers with In-111 at an increasing In-111 to polymer ratio. The polymers show 55-fold to 138-fold higher maximum specific activity than DTPA modified tmFab-SAv. Moreover, the HER2 immunoreactivities of these RICs were evaluated by measuring their specific binding ability toward HER2 overexpressing SKOV-3 ovarian cancer cells. The results demonstrate that although in the presence of polymer there is increased nonspecific binding, HER2 targeting ability was retained, ensuring the radionuclide delivery ability of these RICs.