In vivo targeting function of N-linked oligosaccharides with terminating galactose and N-acetylgalactosamine residues

Ming H Chiu; Toshiaki Tamura; Manpreet S Wadhwa; Kevin G Rice

doi:10.1016/S0021-9258(17)33992-3

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In vivo targeting function of N-linked oligosaccharides with terminating galactose and N-acetylgalactosamine residues

Journal article

Open access

Peer reviewed

In vivo targeting function of N-linked oligosaccharides with terminating galactose and N-acetylgalactosamine residues

Ming H Chiu, Toshiaki Tamura, Manpreet S Wadhwa and Kevin G Rice

The Journal of biological chemistry, Vol.269(23), pp.16195-16202

06/10/1994

DOI: 10.1016/S0021-9258(17)33992-3

PMID: 8206921

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Abstract

N-Linked biantennary, triantennary, and core fucosylated biantennary oligosaccharides were isolated from animal glycoproteins and derivatized at their reducing end with Boc-tyrosine. The terminal Gal residues were enzymatically removed and replaced with GalNAc. Tyrosinamide-oligosaccharides were radioiodinated and administered intravenously to mice. Pharmacokinetic and biodistribution studies revealed structure-dependent differences in the steady-state volume of distribution, total body clearance rate, and targeting efficiency. Tyrosinamide-oligosaccharides were found to resist metabolism relative to a natural triantennary glycopeptide which was rapidly degraded in vivo. Triantennary oligosaccharides containing terminal Gal or Gal-NAc targeted the liver efficiently whereas biantennary oligosaccharides containing terminal Gal residues and differing only in their core fucosylation avoided recognition by the asialoglycoprotein receptor and were cleared unmetabolized by renal filtration. In contrast, biantennary oligosaccharides containing terminal Gal-NAc residues targeted the liver with much greater efficiency than Gal-terminated triantennary oligosaccharide. Core fucosylation reduced the metabolism rate of tyrosinamide-biantennary in the liver. The results establish the utility of tyrosinamide-oligosaccharides as probes to analyze the ligand specificity of mammalian lectins in vivo and demonstrate that a GalNAc-terminated biantennary is a potent ligand for the asialoglycoprotein receptor.

Ligands

Acetylgalactosamine - chemistry

Animals

Asialoglycoprotein Receptor

Biological Transport

Carbohydrate Sequence

Galactose - chemistry

Magnetic Resonance Spectroscopy

Metabolic Clearance Rate

Mice

Mice, Inbred ICR

Molecular Sequence Data

Oligosaccharides - chemistry

Oligosaccharides - pharmacokinetics

Receptors, Cell Surface - metabolism

Spectrometry, Mass, Fast Atom Bombardment

Tissue Distribution

Tyrosine - analogs & derivatives

Tyrosine - chemistry

Details

Title: Subtitle: In vivo targeting function of N-linked oligosaccharides with terminating galactose and N-acetylgalactosamine residues
Creators: Ming H Chiu - The Ohio State University
Toshiaki Tamura - The Ohio State University
Manpreet S Wadhwa - The Ohio State University
Kevin G Rice
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.269(23), pp.16195-16202
DOI: 10.1016/S0021-9258(17)33992-3
PMID: 8206921
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Grant note: DK45742 / NIDDK NIH HHS GM48048 / NIGMS NIH HHS
Language: English
Date published: 06/10/1994
Academic Unit: Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Medicinal and Natural Products Chemistry
Record Identifier: 9984365895102771

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