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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...

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Autores principales: Rossi, Lorenzo, Kerekes, Krisztina, Kovács‐Kocsi, Judit, Körhegyi, Zoltán, Bodnár, Magdolna, Fazekas, Erika, Prépost, Eszter, Pignatelli, Cataldo, Caneva, Enrico, Nicotra, Francesco, Russo, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
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.
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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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