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    Bottom-up and top-down profiling of pentosan polysulfate

    Author
    Lin, Lei; Yu, Yanlei; Zhang, Fuming; Xia, Ke; Zhang, Xing; Linhardt, Robert J.
    ORCID
    https://orcid.org/0000-0003-2219-5833
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    BOTTOM-UP AND TOP-DOWN PROFILING OF PENTOSAN POLYSULFATE.pdf (901.7Kb)
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    Date Issued
    2019-08-21
    Subject
    Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
    Degree
    Terms of Use
    In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/;
    Full Citation
    Bottom-up and top-down profiling of pentosan polysulfate, L. Lin, Y. Yu, F. Zhang, K. Xia, X. Zhang, R. J. Linhardt, Analyst,144, 4781-4786, 2019.
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    URI
    https://hdl.handle.net/20.500.13015/5406; https://doi.org/10.1039/c9an01006h
    Abstract
    Pentosan polysulfate (PPS) is a semi-synthetic glycosaminoglycan (GAG) mimetic. PPS, synthesized through the chemical sulfonation of a plant-derived β-(1 → 4)-xylan, is the active pharmaceutical ingredient of the drug Elmiron™ used to treat interstitial cystitis. Unlike natural GAGs that can be enzymatically broken down into oligosaccharides for analysis, PPS is an unnatural polyanionic polysaccharide and is not amenable to such an analytical approach. Instead reactive oxygen species were used for the controlled depolymerization of PPS and the resulting oligosaccharide fragments were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to obtain bottom-up information on its composition. Because PPS has an average molecular weight ranging from 4000 to 6000 Da, similar to that of low molecular weight heparin, this suggested that it might be possible to use LC-MS on its intact chains and perform top-down analysis. The bottom-up and top-down analysis of PPS provides the first detailed compositional and structural information on PPS. Finally, we examined whether PPS would interfere with polysaccharide lyases and hydrolases, used in the analysis of natural GAGs such as chondroitin sulfates, heparan sulfate, and keratan sulfates. We found that PPS did not interfere with GAG analysis, suggesting that a combination of chemical and enzymatic treatment could be used to analyze samples containing both natural GAGs and PPS.;
    Description
    Analyst,144, 4781-4786; Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
    Department
    The Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
    Publisher
    Royal Society of Chemistry
    Relationships
    The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; Analyst; https://harc.rpi.edu/;
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    A full text version is available in DSpace@RPI;
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