Trivalent, Gal/GalNAc-containing ligands designed for the asialoglycoprotein receptor |
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Authors: | Khorev Oleg Stokmaier Daniela Schwardt Oliver Cutting Brian Ernst Beat |
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Institution: | aInstitute of Molecular Pharmacy, Pharmacenter—University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland |
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Abstract: | 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, β-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. |
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Keywords: | Asialoglycoprotein receptor (ASGP-R) Drug delivery Flow cytometry Fluorescence microscopy Fluorescent probes |
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