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dc.contributor.authorDarwish, Ghassanen_US
dc.contributor.authorHelmerhorst, Eva J.en_US
dc.contributor.authorSchuppan, Detlefen_US
dc.contributor.authorOppenheim, Frank G.en_US
dc.contributor.authorWei, Guoxianen_US
dc.date2019-04-26
dc.date.accessioned2020-05-15T15:57:59Z
dc.date.available2020-05-15T15:57:59Z
dc.date.issued2019-05-16
dc.identifier.citationGhassan 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
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/2144/40919
dc.description.abstractDetoxification 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.en_US
dc.description.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522598/
dc.format.extentp. 7505 - 7515en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofScientific Reports
dc.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/.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBiochemistry and cell biologyen_US
dc.titlePharmaceutically modified subtilisins withstand acidic conditions and effectively degrade gluten in vivoen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41598-019-43837-9
pubs.elements-sourcemanual-entryen_US
pubs.notesCorresponding Author: Guoxian Weien_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Health & Rehabilitation Sciences: Sargent Collegeen_US
pubs.organisational-groupBoston University, College of Health & Rehabilitation Sciences: Sargent College, Physical Therapy and Athletic Trainingen_US
pubs.organisational-groupBoston University, Henry M. Goldman School of Dental Medicineen_US
pubs.publication-statusPublisheden_US
dc.date.online2019-05-16
dc.description.oaversionPublished version
dc.identifier.mycv453157


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© 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/.
Except where otherwise noted, this item's license is described as © 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/.