Design of quaternary chitosan conjugate having antennary galactose residues as a gene delivery tool

Design of quaternary chitosan conjugate having antennary galactose residues as a gene delivery tool
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DOI:
10.1016/s0144-8617(96)00154-3
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发表时间:
1997-02
影响因子:
11.2
通讯作者:
J. Murata;Y. Ohya;T. Ouchi
J. Murata;Y. Ohya;T. Ouchi
中科院分区:
化学1区
文献类型:
--
作者:
J. Murata;Y. Ohya;T. Ouchi

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众所周知,某些糖类物质在细胞表面的生物识别中起着重要的作用。因此,它们有望应用于细胞识别设备。近年来,研究表明,糖簇糖苷在寡糖链与受体的特异性相互作用中发挥着重要作用。由于壳聚糖是一种阳离子天然多糖,具有与DNA形成共价复合物的能力,因此有望在基因传递系统中作为DNA的载体。因此,为了通过受体介导的内吞作用实现有效的基因递送,进行了具有可识别的支链糖残基的新型聚阳离子多糖衍生物,N,N,N-三甲基(TM)-壳聚糖/四半乳糖天线缀合物(TC-Gal 4A 20)的合成。测试了TC-Gal 4A 20偶联物的细胞识别能力,并探讨了其作为基因传递工具的可能性。TC-Gal 4A 20偶联物与RCA 120凝集素具有良好的亲和性,其聚阳离子-DNA复合物具有向肝细胞特异性递送基因的能力。
It is well-known that some kinds of saccharide play the important roles in biological recognition on cellular surface. So, they are expected to be applied for cellular recognition devices. Recently, it was reported that cluster glycosides were effective in the specific interaction between oligosaccharide chains and receptors. Since chitosan is a cationic natural polysaccharide, having formation ability of polyelectrolyte complex with DNA, it is expected to be used as a carrier of DNA in gene delivery systems. So, in order to achieve an efficient gene delivery via receptor-mediated endocytosis, the synthesis of novel polycationic polysaccharide derivative having recognizable branched saccharide residues, N,N,N-trimethyl(TM)-chitosan/tetragalactose antenna conjugate (TC-Gal4A20), was carried out. The cellular recognition ability of TC-Gal4A20 conjugate were tested, and then the possibility of its application as a gene delivery tool was investigated. TC-Gal4A20 conjugate showed high affinity to RCA120lectin and its polycation-DNA complex had the ability of specific gene delivery to hepatocyte.