C-(Stp)2-K(K-((Y)3)2)-(Stp)2-C | 1416015-08-1

• 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: C-(Stp)2-K(K-((Y)3)2)-(Stp)2-C
• CAS: 1416015-08-1
• 化学式: C₁₂₀H₁₉₀N₃₂O₂₅S₂
• 分子量: 2545.16
• InChiKey: BZEOZGNKFFTTAP-HGHUWENJSA-N

反应信息

• 作为反应物：
  描述：

  C-(Stp)2-K(K-((Y)3)2)-(Stp)2-C 、 Nbz-G-PEG₂₄-A 在 4-巯基苯基乙酸 、 盐酸胍 、 三(2-羰基乙基)磷盐酸盐 作用下， 以 aq. phosphate buffer 为溶剂， 生成 C-(Stp)2-K(K-((Y)3)2)-(Stp)2-C-G-PEG₂₄-A
  参考文献：
  名称：

  Native chemical ligation for conversion of sequence-defined oligomers into targeted pDNA and siRNA carriers

  摘要：

  Native chemical ligation (NCL) was established for the conversion of sequence-defined oligomers of different topologies into targeted and PEG shielded pDNA and siRNA carriers. From an existing library of non-targeted oligoethanamino amides, six oligomers containing N-terminal cysteines were selected as cationic cores, to which monodisperse polyethylene glycol (PEG) containing terminal folic acid as targeting ligand (or terminal alanine as targeting negative control ligand) were attached by NCL. Ligated conjugates plus controls (in sum 18 oligomers) were evaluated for pDNA or siRNA gene delivery. Biophysical characteristics including nucleic acid binding in the absence or presence of serum, as well as biological activities in cellular uptake and gene transfer (or gene silencing, respectively) were determined. In most cases, the folic acid-PEG-ligated oligomers displayed a strongly improved cellular binding, uptake and gene transfer into receptor-positive KB cells as compared to the alanine-PEG controls. Changing the topological structures by increasing the number of cationic arms, adding tyrosine trimers as polyplex stabilizing domains, or histidines facilitating endosomal escape resulted in beneficial gene transfer characteristics. The screen revealed different requirements for pDNA and siRNA delivery. A folate-PEG ligated histidinylated four-arm oligomer was most effective for pDNA delivery but inactive for siRNA, whereas a folate-PEG-ligated three-arm oligomer with tyrosine trimer modifications was most effective in siRNA mediated gene silencing. The results demonstrate the site-selective NCL reaction as powerful method to modify existing oligomers. Thus multifunctional targeted carriers can be obtained with ease and used to identify lead structures for subsequent in vivo delivery. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jconrel.2014.02.015