Boston University Libraries OpenBU
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    •   OpenBU
    • BU Open Access Articles
    • BU Open Access Articles
    • View Item
    •   OpenBU
    • BU Open Access Articles
    • BU Open Access Articles
    • View Item

    Pharmaceutically modified subtilisins withstand acidic conditions and effectively degrade gluten in vivo

    Thumbnail
    License
    © The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
    Date Issued
    2019-05-16
    Publisher Version
    10.1038/s41598-019-43837-9
    Author(s)
    Darwish, Ghassan
    Helmerhorst, Eva J.
    Schuppan, Detlef
    Oppenheim, Frank G.
    Wei, Guoxian
    Share to FacebookShare to TwitterShare by Email
    Export Citation
    Download to BibTex
    Download to EndNote/RefMan (RIS)
    Metadata
    Show full item record
    Permanent Link
    https://hdl.handle.net/2144/40919
    OA Version
    Published version
    Citation (published version)
    Ghassan Darwish, Eva J Helmerhorst, Detlef Schuppan, Frank G Oppenheim, Guoxian Wei. 2019. "Pharmaceutically modified subtilisins withstand acidic conditions and effectively degrade gluten in vivo." Scientific Reports, Volume 9, pp. 7505 - 7515. https://doi.org/10.1038/s41598-019-43837-9
    Abstract
    Detoxification of gluten immunogenic epitopes is a promising strategy for the treatment of celiac disease. Our previous studies have shown that these epitopes can be degraded in vitro by subtilisin enzymes derived from Rothia mucilaginosa, a natural microbial colonizer of the oral cavity. The challenge is that the enzyme is not optimally active under acidic conditions as encountered in the stomach. We therefore aimed to protect and maintain subtilisin-A enzyme activity by exploring two pharmaceutical modification techniques: PEGylation and Polylactic glycolic acid (PLGA) microencapsulation. PEGylation of subtilisin-A (Sub-A) was performed by attaching methoxypolyethylene glycol (mPEG, 5 kDa). The PEGylation protected subtilisin-A from autolysis at neutral pH. The PEGylated Sub-A (Sub-A-mPEG) was further encapsulated by PLGA. The microencapsulated Sub-A-mPEG-PLGA showed significantly increased protection against acid exposure in vitro. In vivo, gluten immunogenic epitopes were decreased by 60% in the stomach of mice fed with chow containing Sub-A-mPEG-PLGA (0.2mg Sub-A/ g chow) (n=9) compared to 31.9 % in mice fed with chow containing unmodified Sub-A (n=9). These results show that the developed pharmaceutical modification can protect Sub-A from auto-digestion as well as from acid inactivation, thus rendering the enzyme more effective for applications in vivo.
    Rights
    © The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
    Collections
    • SAR: Physical Therapy & Athletic Training: Scholarly Papers [52]
    • GSDM: Scholarly Works [21]
    • BU Open Access Articles [3732]


    Boston University
    Contact Us | Send Feedback | Help
     

     

    Browse

    All of OpenBUCommunities & CollectionsIssue DateAuthorsTitlesSubjectsThis CollectionIssue DateAuthorsTitlesSubjects

    Deposit Materials

    LoginNon-BU Registration

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Boston University
    Contact Us | Send Feedback | Help