Evidence for an asialoglycoprotein receptor on nonparenchymal cells for O-linked glycoproteins

The Journal of Pharmacology and Experimental Therapeutics
Eric G StefanichPaul J Fielder

Abstract

B cell-activating factor receptor 3 (BR3)-Fc is an IgG1-receptor dimeric fusion protein that has multiple O-linked glycosylation sites and sialylation levels that can vary in the manufacturing process. Increased sialic acid levels resulted from increased site occupancy with the O-linked N-acetylgalactosamine (GalNAc-Gal), but because the ratio of sialic acid per mole of oligosaccharide remained approximately 1, this led to increased asialo terminal GalNAc. Previous studies have demonstrated an effect of terminal asialo Gal or GalNAc on the clearance of glycoproteins due to uptake and degradation by lectin receptors in the liver. However, the previous studies examined N-linked oligosaccharides, and there are less data regarding O-linked oligosaccharides. The objective of these studies was to determine the effects on the pharmacokinetics and distribution of the asialo terminal GalNAc and varying amounts of sialic acid residues on BR3-Fc. The results of the data presented here suggest that exposed Gal on the desialylated BR3-Fc led to rapid clearance due to uptake and degradation in the liver that was associated with nonparenchymal cells. It is interesting to note that the data indicated a decreased clearance and increased exposur...Continue Reading

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Citations

Dec 7, 2011·ACS Chemical Biology·Lai-Xi Wang, Joseph V Lomino
Nov 7, 2009·Current Opinion in Biotechnology·Huijuan Li, Marc d'Anjou
May 7, 2016·Journal of Bioscience and Bioengineering·Shunsuke KidaniShinji Iijima
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Mar 12, 2021·Biochemical Society Transactions·Roberto DoniniCleo Kontoravdi
Jun 12, 2020·ACS Synthetic Biology·Weston KightlingerMichael C Jewett

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