1. Analysis of 3
- Author
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Zhangjie Wang, Katelyn Arnold, Vijay M. Dhurandahare, Yongmei Xu, Vijayakanth Pagadala, Erick Labra, Walter Jeske, Jawed Fareed, Marla Gearing, and Jian Liu
- Subjects
Mice ,Sheep ,Sulfates ,Swine ,Tandem Mass Spectrometry ,Animals ,Humans ,Oligosaccharides ,Cattle ,Heparitin Sulfate ,Article ,Analytical Chemistry ,Chromatography, Liquid - Abstract
The 3-O-sulfated glucosamine in heparan sulfate (HS) is a low-abundance structural component, but it is a key saccharide unit for the biological activities of HS. A method to determine the level of 3-O-sulfated HS is lacking. Here, we describe a LC–MS/MS based method to analyze the structural motifs. We determined the levels of 3-O-sulfated structural motifs from pharmaceutical heparin manufactured from bovine, porcine, and ovine. We discovered that saccharide chains carrying 3-O-sulfation from enoxaparin, an FDA-approved low-molecular weight heparin, displayed a slower clearance rate than non-3-O-sulfated sugar chains in a mouse model. Lastly, we detected the 3-O-sulfated HS from human brain. Furthermore, we found that a specific 3-O-sulfated structural motif, tetra-1, is elevated in the brain HS from Alzheimer’s disease patients (n = 5, p = 0.0020). Our method offers a practical solution to measure 3-O-sulfated HS from biological sources with the sensitivity and quantitative capability.
- Published
- 2023