Details

Autor(en) / Beteiligte

• Rossi, Lorenzo
• Kerekes, Krisztina
• Kovács‐Kocsi, Judit
• Körhegyi, Zoltán
• Bodnár, Magdolna
• Fazekas, Erika
• Prépost, Eszter
• Pignatelli, Cataldo
• Caneva, Enrico
• Nicotra, Francesco
• Russo, Laura

Titel

Multivalent γ‐PGA‐Exendin‐4 Conjugates to Target Pancreatic β‐Cells

Ist Teil von

• Chembiochem : a European journal of chemical biology, 2022-09, Vol.23 (17), p.e202200196-n/a

Ort / Verlag

Weinheim: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. Exendin‐4‐γ‐polyglutamic acid conjugates have been generated by efficient Diels‐Alder click reaction. The highly functionalized conjugate (average 106 Exendin‐4 molecules/γ‐Polyglutamic acid) showed affinity towards GLP1 receptor higher with respect to Enendin‐4 a labile peptide approved for type 2 diabetes treatment.