Autor: Kostadinova, K. A.; Venne, J. L.; Krajcovicova, S.*; Dodgson, J.; Hogendorf, W. F. J.; Nielsen, T. E. D.; Hymel, D.; Bolt, H.; Collinson, A.; Revell, J.; Spring, D. R.
Název práce v češtině: –
Název práce v angličtině: Peptide Marriages: Modular Assembly of Multi-Agonist Therapeutics
Studentská publikace: ne
Klíčová slova v češtině: –
Klíčová slova v angličtině: amycretin; dual peptide agonists; peptide therapeutics; semaglutide; solid-phase synthesis
Abstrakt česky: –
Abstrakt anglicky: Multi-receptor peptide agonists represent an effective strategy for obesity treatment, extending the success of incretin-based therapies through simultaneous engagement of complementary targets. Their development, however, is synthetically demanding, as each receptor combination typically requires de novo preparation of large fusion peptides. We report a modular polyethylene glycol (PEG)-based scaffold that enables orthogonal attachment of up to three functional components, including therapeutic peptides, half-life–extending units, and other labels, via sequential strain-promoted azide–alkyne cycloaddition (SPAAC) and copper-catalysed azide–alkyne cycloaddition (CuAAC). The scaffold is assembled on solid phase without intermediate purification, providing a readily accessible and versatile linker. Using glucagon-like peptide-1 (GLP-1) and amylin receptor agonists as a proof-of-concept, dual-agonist constructs with tuneable valency and functionality were rapidly generated. Lead conjugates displayed balanced, low-picomolar potency at both receptors in cyclic adenosine monophosphate (cAMP) assays and showed selective receptor-mediated internalisation in GLP-1 receptor-expressing cells. This orthogonal click-based platform enables rapid and modular multi-agonist assembly, facilitating systematic exploration of receptor combinations, valency, and payload effects. Beyond incretin biology, it offers a general route to multifunctional peptide therapeutics and diagnostics.
Jazyk v originále: english
Název časopisu: Chem. Eur. J.
Rok: 2026
Svazek (ročník): –
Číslo časopisu v rámci uvedeného svazku: –
Strana od-do: e71280
Impact factor: 3.6
Q1: ne

ISSN časopisu: –
Vydavatel: Wiley
Způsob financování: 22-07138O
DOI: https://doi.org/10.1002/chem.71280