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.

Rossi, L., Kerekes, K., Kovacs-Kocsi, J., Korhegyi, Z., Bodnar, M., Fazekas, E., et al. (2022). Multivalent γ-PGA-Exendin-4 Conjugates to Target Pancreatic β-Cells. CHEMBIOCHEM [10.1002/cbic.202200196].

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

Rossi L.;Pignatelli C.;Nicotra F.;Russo L.
2022

Abstract

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.
Si
Articolo in rivista - Articolo scientifico
Scientifica
beta-cell targeting; diabetes; exendin-4; GLP-1R; pancreatic tumor; poly-gamma-glutamic acid;
English
Rossi, L., Kerekes, K., Kovacs-Kocsi, J., Korhegyi, Z., Bodnar, M., Fazekas, E., et al. (2022). Multivalent γ-PGA-Exendin-4 Conjugates to Target Pancreatic β-Cells. CHEMBIOCHEM [10.1002/cbic.202200196].
Rossi, L; Kerekes, K; Kovacs-Kocsi, J; Korhegyi, Z; Bodnar, M; Fazekas, E; Prepost, E; Pignatelli, C; Caneva, E; Nicotra, F; Russo, L
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/390586
Citazioni
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
Social impact