A new N-acetylgalactosamine containing peptide as a targeting vehicle for mammalian hepatocytes via asialoglycoprotein receptor endocytosis.

Ying Ta Wu, Weir Torn Jiaang, Kuo Ging Lin, Chun Ming Huang, Chin Hsien Chang, Ying Ling Sun, Kuo Hsien Fan, Wei Chuan Hsu, Hsin Ell Wang, Shwu Bin Lin, Shui Tein Chen

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)119-127
Number of pages9
JournalCurrent drug delivery
Volume1
Issue number2
DOIs
StatePublished - Apr 2004

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