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Multivalent γ‐PGA‐Exendin‐4 Conjugates to Target Pancreatic β‐Cells
Targeting of glucagon‐like peptide 1 receptor (GLP‐1R), expressed on the surface of pancreatic β‐cells, is of great interest for the development of advanced therapies for diabetes and diagnostics for insulinoma. We report the conjugation of exendin‐4 (Ex‐4), an approved drug to treat type 2 diabetes...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542156/ https://www.ncbi.nlm.nih.gov/pubmed/35762648 http://dx.doi.org/10.1002/cbic.202200196 |
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author | Rossi, Lorenzo Kerekes, Krisztina Kovács‐Kocsi, Judit Körhegyi, Zoltán Bodnár, Magdolna Fazekas, Erika Prépost, Eszter Pignatelli, Cataldo Caneva, Enrico Nicotra, Francesco Russo, Laura |
author_facet | Rossi, Lorenzo Kerekes, Krisztina Kovács‐Kocsi, Judit Körhegyi, Zoltán Bodnár, Magdolna Fazekas, Erika Prépost, Eszter Pignatelli, Cataldo Caneva, Enrico Nicotra, Francesco Russo, Laura |
author_sort | Rossi, Lorenzo |
collection | PubMed |
description | Targeting of glucagon‐like peptide 1 receptor (GLP‐1R), expressed on the surface of pancreatic β‐cells, is of great interest for the development of advanced therapies for diabetes and diagnostics for insulinoma. We report the conjugation of exendin‐4 (Ex‐4), an approved drug to treat type 2 diabetes, to poly‐γ‐glutamic acid (γ‐PGA) to obtain more stable and effective GLP‐1R ligands. Exendin‐4 modified at Lysine‐27 with PEG4‐maleimide was conjugated to γ‐PGA functionalized with furan, in different molar ratios, exploiting a chemoselective Diels‐Alder cycloaddition. The γ‐PGA presenting the highest number of conjugated Ex‐4 molecules (average 120 per polymeric chain) showed a double affinity towards GLP‐1R with respect to exendin per se, paving the way to improved therapeutic and diagnostic applications. |
format | Online Article Text |
id | pubmed-9542156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95421562022-10-14 Multivalent γ‐PGA‐Exendin‐4 Conjugates to Target Pancreatic β‐Cells Rossi, Lorenzo Kerekes, Krisztina Kovács‐Kocsi, Judit Körhegyi, Zoltán Bodnár, Magdolna Fazekas, Erika Prépost, Eszter Pignatelli, Cataldo Caneva, Enrico Nicotra, Francesco Russo, Laura Chembiochem Research Articles Targeting of glucagon‐like peptide 1 receptor (GLP‐1R), expressed on the surface of pancreatic β‐cells, is of great interest for the development of advanced therapies for diabetes and diagnostics for insulinoma. We report the conjugation of exendin‐4 (Ex‐4), an approved drug to treat type 2 diabetes, to poly‐γ‐glutamic acid (γ‐PGA) to obtain more stable and effective GLP‐1R ligands. Exendin‐4 modified at Lysine‐27 with PEG4‐maleimide was conjugated to γ‐PGA functionalized with furan, in different molar ratios, exploiting a chemoselective Diels‐Alder cycloaddition. The γ‐PGA presenting the highest number of conjugated Ex‐4 molecules (average 120 per polymeric chain) showed a double affinity towards GLP‐1R with respect to exendin per se, paving the way to improved therapeutic and diagnostic applications. John Wiley and Sons Inc. 2022-07-13 2022-09-05 /pmc/articles/PMC9542156/ /pubmed/35762648 http://dx.doi.org/10.1002/cbic.202200196 Text en © 2022 The Authors. ChemBioChem published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Rossi, Lorenzo Kerekes, Krisztina Kovács‐Kocsi, Judit Körhegyi, Zoltán Bodnár, Magdolna Fazekas, Erika Prépost, Eszter Pignatelli, Cataldo Caneva, Enrico Nicotra, Francesco Russo, Laura Multivalent γ‐PGA‐Exendin‐4 Conjugates to Target Pancreatic β‐Cells |
title | Multivalent γ‐PGA‐Exendin‐4 Conjugates to Target Pancreatic β‐Cells |
title_full | Multivalent γ‐PGA‐Exendin‐4 Conjugates to Target Pancreatic β‐Cells |
title_fullStr | Multivalent γ‐PGA‐Exendin‐4 Conjugates to Target Pancreatic β‐Cells |
title_full_unstemmed | Multivalent γ‐PGA‐Exendin‐4 Conjugates to Target Pancreatic β‐Cells |
title_short | Multivalent γ‐PGA‐Exendin‐4 Conjugates to Target Pancreatic β‐Cells |
title_sort | multivalent γ‐pga‐exendin‐4 conjugates to target pancreatic β‐cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542156/ https://www.ncbi.nlm.nih.gov/pubmed/35762648 http://dx.doi.org/10.1002/cbic.202200196 |
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