Improving the Sensitivity for Quantifying Heparan Sulfate from Biological Samples

Heparan sulfates (HSs) are widely expressed glycans in the animal kingdom. HS plays a role in regulating cell differentiation/proliferation, embryonic development, blood coagulation, inflammatory response, and viral infection. The amount of HS and its structural information are critically important...

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Bibliographic Details
Published inAnalytical chemistry (Washington) Vol. 93; no. 32; pp. 11191 - 11199
Main Authors Wang, Zhangjie, Dhurandhare, Vijay M, Mahung, Cressida A, Arnold, Katelyn, Li, Jine, Su, Guowei, Xu, Ding, Maile, Rob, Liu, Jian
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 17.08.2021
Subjects
Acetaminophen
Animal diseases
Animal models
Animals
Biological properties
Biological samples
Biomarkers
Blood coagulation
Cell differentiation
Chemistry
Chromatography, Liquid
Differentiation (biology)
Disaccharides
Embryogenesis
Embryonic growth stage
Heparan sulfate
Heparitin Sulfate
In vivo methods and tests
Inflammation
Inflammatory response
Mice
Organs
Polysaccharides
Prognosis
Quinoline
Reagents
Sulfates
Tandem Mass Spectrometry
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Summary:Heparan sulfates (HSs) are widely expressed glycans in the animal kingdom. HS plays a role in regulating cell differentiation/proliferation, embryonic development, blood coagulation, inflammatory response, and viral infection. The amount of HS and its structural information are critically important for investigating the functions of HS in vivo. A sensitive and reliable quantitative technique for the analysis of HS from biological samples is under development. Here, we report a new labeling reagent for HS disaccharides analysis, 6-amino-N-(2-diethylamino)­ethyl quinoline-2-carboamide (AMQC). The AMQC-conjugated disaccharides are analyzed by LC-MS/MS in positive mode, significantly improving the sensitivity. The use of AMQC coupled with authentic 13C-labeled HS disaccharide internal standards empowered us to determine the amount and the disaccharide composition of the HS on a single histological slide. We used this method to profile the levels of HS in the plasma/serum and tissues/organs to assist the disease prognosis in two animal models, including the acetaminophen (APAP)-induced acute liver injury mouse model and the burn injury mouse model. The method may uncover the roles of HS contributing to the diseases as well as provide a potential new set of biomarkers for disease diagnosis and prognosis.
Bibliography:Z.W. completed the analysis of HS from tissues. V.M.D. synthesized AMQC tag for disaccharide analysis. C.A.M. and R.M. prepared the tissue samples from the burn mice model. K.A. prepared the tissue samples from APAP-injured mice. Jine Li and D.X. provided histological slide samples. G.S. offered the design of the scheme for the synthesis of AMQC. Jian Liu and Z.W. designed the project and wrote the manuscript. All authors read the manuscript and agreed with the contents.
Author Contributions
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.1c01761