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Glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems
The glycosylation of recombinant β-glucocerebrosidase, and in particular the exposure of mannose residues, has been shown to be a key factor in the success of ERT (enzyme replacement therapy) for the treatment of GD (Gaucher disease). Macrophages, the target cells in GD, internalize β-glucocerebrosi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782720/ https://www.ncbi.nlm.nih.gov/pubmed/23980545 http://dx.doi.org/10.1042/BSR20130081 |
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author | Tekoah, Yoram Tzaban, Salit Kizhner, Tali Hainrichson, Mariana Gantman, Anna Golembo, Myriam Aviezer, David Shaaltiel, Yoseph |
author_facet | Tekoah, Yoram Tzaban, Salit Kizhner, Tali Hainrichson, Mariana Gantman, Anna Golembo, Myriam Aviezer, David Shaaltiel, Yoseph |
author_sort | Tekoah, Yoram |
collection | PubMed |
description | The glycosylation of recombinant β-glucocerebrosidase, and in particular the exposure of mannose residues, has been shown to be a key factor in the success of ERT (enzyme replacement therapy) for the treatment of GD (Gaucher disease). Macrophages, the target cells in GD, internalize β-glucocerebrosidase through MRs (mannose receptors). Three enzymes are commercially available for the treatment of GD by ERT. Taliglucerase alfa, imiglucerase and velaglucerase alfa are each produced in different cell systems and undergo various post-translational or post-production glycosylation modifications to expose their mannose residues. This is the first study in which the glycosylation profiles of the three enzymes are compared, using the same methodology and the effect on functionality and cellular uptake is evaluated. While the major differences in glycosylation profiles reside in the variation of terminal residues and mannose chain length, the enzymatic activity and stability are not affected by these differences. Furthermore, the cellular uptake and in-cell stability in rat and human macrophages are similar. Finally, in vivo studies to evaluate the uptake into target organs also show similar results for all three enzymes. These results indicate that the variations of glycosylation between the three regulatory-approved β-glucocerebrosidase enzymes have no effect on their function or distribution. |
format | Online Article Text |
id | pubmed-3782720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-37827202013-09-25 Glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems Tekoah, Yoram Tzaban, Salit Kizhner, Tali Hainrichson, Mariana Gantman, Anna Golembo, Myriam Aviezer, David Shaaltiel, Yoseph Biosci Rep Original Paper The glycosylation of recombinant β-glucocerebrosidase, and in particular the exposure of mannose residues, has been shown to be a key factor in the success of ERT (enzyme replacement therapy) for the treatment of GD (Gaucher disease). Macrophages, the target cells in GD, internalize β-glucocerebrosidase through MRs (mannose receptors). Three enzymes are commercially available for the treatment of GD by ERT. Taliglucerase alfa, imiglucerase and velaglucerase alfa are each produced in different cell systems and undergo various post-translational or post-production glycosylation modifications to expose their mannose residues. This is the first study in which the glycosylation profiles of the three enzymes are compared, using the same methodology and the effect on functionality and cellular uptake is evaluated. While the major differences in glycosylation profiles reside in the variation of terminal residues and mannose chain length, the enzymatic activity and stability are not affected by these differences. Furthermore, the cellular uptake and in-cell stability in rat and human macrophages are similar. Finally, in vivo studies to evaluate the uptake into target organs also show similar results for all three enzymes. These results indicate that the variations of glycosylation between the three regulatory-approved β-glucocerebrosidase enzymes have no effect on their function or distribution. Portland Press Ltd. 2013-09-25 /pmc/articles/PMC3782720/ /pubmed/23980545 http://dx.doi.org/10.1042/BSR20130081 Text en © 2013 The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Licence (CC-BY)(http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Paper Tekoah, Yoram Tzaban, Salit Kizhner, Tali Hainrichson, Mariana Gantman, Anna Golembo, Myriam Aviezer, David Shaaltiel, Yoseph Glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems |
title | Glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems |
title_full | Glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems |
title_fullStr | Glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems |
title_full_unstemmed | Glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems |
title_short | Glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems |
title_sort | glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782720/ https://www.ncbi.nlm.nih.gov/pubmed/23980545 http://dx.doi.org/10.1042/BSR20130081 |
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