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 language | English |
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Pages (from-to) | 119-127 |
Number of pages | 9 |
Journal | Current drug delivery |
Volume | 1 |
Issue number | 2 |
DOIs | |
State | Published - Apr 2004 |