posted on 2022-02-02, 17:13authored byZhangjie Wang, Katelyn Arnold, Vijay M. Dhurandahare, Yongmei Xu, Vijayakanth Pagadala, Erick Labra, Walter Jeske, Jawed Fareed, Marla Gearing, Jian Liu
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.