A New N-Acetylgalactosamine Containing Peptide as a Targeting Vehicle for Mammalian Hepatocytes Via Asialoglycoprotein Receptor Endocytosis
| Autor: | Wei Chuan Hsu, Ying Ling Sun, Hsin Ell Wang, Weir Torn Jiaang, Ying-Ta Wu, Shui-Tein Chen, Chun Ming Huang, Chin Hsien Chang, Kuo Hsien Fan, Shwu Bin Lin, Kuo Ging Lin |
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| Rok vydání: | 2004 |
| Předmět: |
Acetylgalactosamine
Chemistry Pharmaceutical Pharmaceutical Science Peptide Asialoglycoprotein Receptor Biology Kidney Ligands Endocytosis Mice chemistry.chemical_compound Biotin In vivo Cell Line Tumor Peptide synthesis Animals Humans Tissue Distribution Fluorescein chemistry.chemical_classification Drug Carriers Mice Inbred BALB C Glycopeptides Rats Inbred F344 In vitro Rats chemistry Biochemistry Hepatocytes Asialoglycoprotein receptor |
| Zdroj: | Current Drug Delivery. 1:119-127 |
| ISSN: | 1567-2018 |
| DOI: | 10.2174/1567201043479939 |
| Popis: | Galactoside-containing cluster ligands have high affinity for asialoglycoprotein receptors (ASGP-r), which are found in abundance in mammalian parenchymal liver cells. These ligands may be conjugated with a therapeutic drug to improve the efficiency of delivery to diseased liver cells. This report describes a new synthetic route towards clustering glycopeptides containing N-acetyl-D-galactosamine (GalNAc). The building block Fmoc-alpha-(ah-Ac3GalNAc)-L-glutamate allowed access to the target compound YEEE(alpha-ah-GalNAc)(3), a structural mimic of YEE(ah-GalNAc)(3), via solid phase peptide synthesis (SPPS). Fatty acid, poly-lysine, fluorescein and biotin conjugates further demonstrate the facility of the described method. Using fluorescein labeling and 131I labeling, in vitro and in vivo assays confirmed that YEEE(alpha-ah-GalNAc)(3) possesses both specificity and affinity to the liver, similar to the agent YEE(ah-GalNAc)(3), which targets liver lesions. The synthesis described in this report represents a considerable improvement in synthesizing a ligand for ASGP-r by simplifying both the preparation of the starting material and the procedure for conjugating the galactosidase cluster to drugs. |
| Databáze: | OpenAIRE |
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