Trivalent, Gal/GalNAc-containing ligands designed for the asialoglycoprotein receptor
Trivalent, Gal/GalNAc-containing ligands designed for the asialoglycoprotein receptor
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DOI：
10.1016/j.bmc.2008.03.017
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发表时间：
2008-05-01
影响因子：
3.5
通讯作者：
Ernst, Beat
中科院分区：
文献类型：
--
作者：
Khorev, Oleg;Stokmaier, Daniela;Ernst, Beat
设计了一系列与去唾液酸糖蛋白受体(ASGP-R)具有高亲和力和特异性的新型荧光配体，并在人肝细胞上进行了测试。这些化合物含有三个非还原的、β-连接的Gal或GalNAc部分，连接到柔性间隔物上，以实现与ASGP-R结合位点的最佳空间相互作用。最终的构建体被来自实质性肝细胞的HepG2细胞选择性地内吞--这是人类主要的肝细胞类型--在荧光显微镜下可视化的过程。此外，用流式细胞仪对内化过程进行了分析，表明该过程是由受体介导的和选择性的。这项工作中所描述的化合物可以作为研究肝脏内吞作用的有价值的工具，并且适合作为定点药物输送到肝脏的载体。(C)2008爱思唯尔有限公司。保留所有权利。
A series of novel, fluorescent ligands designed to bind with high affinity and specificity to the asialoglycoprotein receptor (ASGP-R) has been synthesized and tested on human liver cells. The compounds bear three non-reducing, beta-linked Gal or GalNAc moieties linked to flexible spacers for an optimal spatial interaction with the binding site of the ASGP-R. The final constructs were selectively endocytosed by HepG2 cells derived from parenchymal liver cells-the major human liver cell type-in a process that was visualized with the aid of fluorescence microscopy. Furthermore, the internalization was analyzed with flow cytometry, which showed the process to be receptor-mediated and selective. The compounds described in this work could serve as valuable tools for studying hepatic endocytosis, and are suited as carriers for site-specific drug delivery to the liver. (C) 2008 Elsevier Ltd. All rights reserved.