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Updated: Sep 29, 2025

Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
Published on: September 13, 2013
Development of disulfide-functionalized peptides covalently binding G protein-coupled receptors
Jürgen Einsiedel1, Maximilian F Schmidt1, Harald Hübner1
1Department of Chemistry and Pharmacy, Medicinal Chemistry, Friedrich-Alexander Universität Erlangen-Nürnberg, Nikolaus-Fiebiger-Straße 10, D-91058 Erlangen, Germany.
Abstract:
A broadly applicable synthesis of peptides incorporating mixed disulfides between cysteine and homocysteine and cysteamine was developed. The method was established using pharmacologically relevant G protein-coupled receptor (GPCR) ligands including the μ-receptor agonist Dmt-DALDA and extended to the orexin derivative Oxa(17-33) and NT(8-13), the C-terminal hexapeptide of neurotensin. The newly developed NT(8-13) analog 6b incorporating an S-functionalized homocysteine revealed covalent binding of the neurotensin receptor 1 (NTSR1) in a radioligand depletion study.
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