N-tert-butoxycarbonyl-N'-acryloyl-cystamine | 1233810-79-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-tert-butoxycarbonyl-N'-acryloyl-cystamine
• CAS: 1233810-79-1
• 化学式: C₁₂H₂₂N₂O₃S₂
• 分子量: 306.45
• InChiKey: FVNDLYSTELBRNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.19
• 重原子数：
  19.0
• 可旋转键数：
  8.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  67.43
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  二碳酸二叔丁酯 在 三乙胺 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 25.5h， 生成 N-tert-butoxycarbonyl-N'-acryloyl-cystamine
  参考文献：
  名称：

  Branched Polyethylenimine Derivatives with Reductively Cleavable Periphery for Safe and Efficient In Vitro Gene Transfer

  摘要：

  Twenty-five kDa polyethylenimine (PEI) is one of the most efficient nonviral gene transfer agents currently applied as a golden standard for in vitro transfection. In this study, novel 25 k Da PEI derivatives with reductively cleavable cystamine periphery (PEI-Cys) were designedto reduce carrier-associated cytotoxicity and to enhance further the transfection activity. The Michael-type conjugate addition of 25 kDa PEI with N-tert-butoxycarbonyl-N'-acryloyl-cystamine (Ac-Cys-Boc) and N-tert-butoxycarbonyl-a-methacryloyl-cystamine (MAc-Cys-Boc) followed by deprotection readily afforded PEI-Cys derivatives, denoted as PEI-(Cys)x(Ac) and PEI-(Cys)x(MAc), with degree of substitution (DS) ranging from 14 to 34 and 13 to 38, respectively. All PEI-Cys derivatives had higher buffer capacity than the parent 25 kDa PEI (21.2 to 23.1% versus 15.1%). Gel retardation and ethidium bromide exclusion assays showed that cystamine modification resulted in largely enhanced interactions with DNA. PEI-(Cys)x(Ac) could condense DNA into small-sized particles of 80-90 nm at and above am N/P ratio of 5/1, which were smaller than polyplexes of 25 kDa PEI (100-130 nm). in comparison, PEI-(Cys)x(MAc) condensed DNA into somewhat larger particles (100-180 nm at N/P ratios from 30/1 to 5/1). Gel retardation and dynamic light scattering (DLS) measurements showed that PEI-Cys polyplexes were quickly unpacked to release DNA in response to 10 mM dithiothreitol (DTT). These PEI-Cys derivatives revealed markedly decreased cytotoxicity as compared with 25 kDa PEI with IC50 values of > 100 mg/L and 50-75 mg/L for HeLa and 293T cells, respectively (corresponding IC50 data of 25 kDa PEI are ca. 11 and 3 mg/L). The in vitro transfection experiments in HeLa and 293T cells using pGL3 as a reporter gene showed that-gene transfection activity of PEI-Cys derivatives decreased with increasing DS and PEI-(Cys)x(MAc) exhibited higher transfection activity than PEI-(Cys)x(Ac) at similar IDS: Notably, polyplexes of PEI-(Cys) 14(Ac) and PEI-(Cys) 13(MAc) showed significantly enhanced gene transfection efficiency (up to 4.1-fold) as compared with 25 IcDa PEI formulation at an N/P ratio of 10/1 in both senum-free and 10% serum-containing conditions. The modification of PEI with reductively cleavable periphery appears to be a potential approach to develop safer and more efficient nonviral gene vectors.

  DOI：

  10.1021/bm101364f