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Products of Chemoenzymatic Synthesis Representing MUC1 Tandem Repeat Unit with T-, ST- or STn-antigen Revealed Distinct Specificities of Anti-MUC1 Antibodies

Anti-mucin1 (MUC1) antibodies have long been used clinically in cancer diagnosis and therapy and specific bindings of some of them are known to be dependent on the differential glycosylation of MUC1. However, a systematic comparison of the binding specificities of anti-MUC1 antibodies was not previo...

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Autores principales: Yoshimura, Yayoi, Denda-Nagai, Kaori, Takahashi, Yoshie, Nagashima, Izuru, Shimizu, Hiroki, Kishimoto, Toshimitsu, Noji, Miki, Shichino, Shigeyuki, Chiba, Yasunori, Irimura, Tatsuro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851390/
https://www.ncbi.nlm.nih.gov/pubmed/31719620
http://dx.doi.org/10.1038/s41598-019-53052-1
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author Yoshimura, Yayoi
Denda-Nagai, Kaori
Takahashi, Yoshie
Nagashima, Izuru
Shimizu, Hiroki
Kishimoto, Toshimitsu
Noji, Miki
Shichino, Shigeyuki
Chiba, Yasunori
Irimura, Tatsuro
author_facet Yoshimura, Yayoi
Denda-Nagai, Kaori
Takahashi, Yoshie
Nagashima, Izuru
Shimizu, Hiroki
Kishimoto, Toshimitsu
Noji, Miki
Shichino, Shigeyuki
Chiba, Yasunori
Irimura, Tatsuro
author_sort Yoshimura, Yayoi
collection PubMed
description Anti-mucin1 (MUC1) antibodies have long been used clinically in cancer diagnosis and therapy and specific bindings of some of them are known to be dependent on the differential glycosylation of MUC1. However, a systematic comparison of the binding specificities of anti-MUC1 antibodies was not previously conducted. Here, a total of 20 glycopeptides including the tandem repeat unit of MUC1, APPAHGVTSAPDTRPAPGSTAPPAHGV with GalNAc (Tn-antigen), Galβ1-3GalNAc (T-antigen), NeuAcα2-3Galβ1-3GalNAc (sialyl-T-antigen), or NeuAcα2-6GalNAc (sialyl-Tn-antigen) at each threonine or serine residue were prepared by a combination of chemical glycopeptide synthesis and enzymatic extension of carbohydrate chains. These glycopeptides were tested by the enzyme-linked immunosorbent assay (ELISA) for their capacity to bind 13 monoclonal antibodies (mAbs) known to be specific for MUC1. The results indicated that anti-MUC1 mAbs have diverse specificities but can be classified into a few characteristic groups based on their binding pattern toward glycopeptides in some cases having a specific glycan at unique glycosylation sites. Because the clinical significance of some of these antibodies was already established, the structural features identified by these antibodies as revealed in the present study should provide useful information relevant to their further clinical use and the biological understanding of MUC1.
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spelling pubmed-68513902019-11-19 Products of Chemoenzymatic Synthesis Representing MUC1 Tandem Repeat Unit with T-, ST- or STn-antigen Revealed Distinct Specificities of Anti-MUC1 Antibodies Yoshimura, Yayoi Denda-Nagai, Kaori Takahashi, Yoshie Nagashima, Izuru Shimizu, Hiroki Kishimoto, Toshimitsu Noji, Miki Shichino, Shigeyuki Chiba, Yasunori Irimura, Tatsuro Sci Rep Article Anti-mucin1 (MUC1) antibodies have long been used clinically in cancer diagnosis and therapy and specific bindings of some of them are known to be dependent on the differential glycosylation of MUC1. However, a systematic comparison of the binding specificities of anti-MUC1 antibodies was not previously conducted. Here, a total of 20 glycopeptides including the tandem repeat unit of MUC1, APPAHGVTSAPDTRPAPGSTAPPAHGV with GalNAc (Tn-antigen), Galβ1-3GalNAc (T-antigen), NeuAcα2-3Galβ1-3GalNAc (sialyl-T-antigen), or NeuAcα2-6GalNAc (sialyl-Tn-antigen) at each threonine or serine residue were prepared by a combination of chemical glycopeptide synthesis and enzymatic extension of carbohydrate chains. These glycopeptides were tested by the enzyme-linked immunosorbent assay (ELISA) for their capacity to bind 13 monoclonal antibodies (mAbs) known to be specific for MUC1. The results indicated that anti-MUC1 mAbs have diverse specificities but can be classified into a few characteristic groups based on their binding pattern toward glycopeptides in some cases having a specific glycan at unique glycosylation sites. Because the clinical significance of some of these antibodies was already established, the structural features identified by these antibodies as revealed in the present study should provide useful information relevant to their further clinical use and the biological understanding of MUC1. Nature Publishing Group UK 2019-11-12 /pmc/articles/PMC6851390/ /pubmed/31719620 http://dx.doi.org/10.1038/s41598-019-53052-1 Text en © 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/.
spellingShingle Article
Yoshimura, Yayoi
Denda-Nagai, Kaori
Takahashi, Yoshie
Nagashima, Izuru
Shimizu, Hiroki
Kishimoto, Toshimitsu
Noji, Miki
Shichino, Shigeyuki
Chiba, Yasunori
Irimura, Tatsuro
Products of Chemoenzymatic Synthesis Representing MUC1 Tandem Repeat Unit with T-, ST- or STn-antigen Revealed Distinct Specificities of Anti-MUC1 Antibodies
title Products of Chemoenzymatic Synthesis Representing MUC1 Tandem Repeat Unit with T-, ST- or STn-antigen Revealed Distinct Specificities of Anti-MUC1 Antibodies
title_full Products of Chemoenzymatic Synthesis Representing MUC1 Tandem Repeat Unit with T-, ST- or STn-antigen Revealed Distinct Specificities of Anti-MUC1 Antibodies
title_fullStr Products of Chemoenzymatic Synthesis Representing MUC1 Tandem Repeat Unit with T-, ST- or STn-antigen Revealed Distinct Specificities of Anti-MUC1 Antibodies
title_full_unstemmed Products of Chemoenzymatic Synthesis Representing MUC1 Tandem Repeat Unit with T-, ST- or STn-antigen Revealed Distinct Specificities of Anti-MUC1 Antibodies
title_short Products of Chemoenzymatic Synthesis Representing MUC1 Tandem Repeat Unit with T-, ST- or STn-antigen Revealed Distinct Specificities of Anti-MUC1 Antibodies
title_sort products of chemoenzymatic synthesis representing muc1 tandem repeat unit with t-, st- or stn-antigen revealed distinct specificities of anti-muc1 antibodies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851390/
https://www.ncbi.nlm.nih.gov/pubmed/31719620
http://dx.doi.org/10.1038/s41598-019-53052-1
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