Deutsch
 
Benutzerhandbuch Datenschutzhinweis Impressum Kontakt
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT

Freigegeben

Zeitschriftenartikel

Potent prearranged positive allosteric modulators of the glucagon-like peptide-1 receptor

MPG-Autoren
/persons/resource/persons208663

Broichhagen,  Johannes
Chemical Biology, Max Planck Institute for Medical Research, Max Planck Society;

Volltexte (frei zugänglich)
Es sind keine frei zugänglichen Volltexte verfügbar
Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Jones, B. J., Scopelliti, R., Tomas, A., Bloom, S. R., Hodson, D. J., & Broichhagen, J. (2017). Potent prearranged positive allosteric modulators of the glucagon-like peptide-1 receptor. ChemistryOpen, 6(4), 501-505. doi:10.1002/open.201700062.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-002D-C81F-7
Zusammenfassung
Drugs that allosterically modulate G protein-coupled receptor (GPCR) activity display higher specificity and may improve disease treatment. However, the rational design of compounds that target the allosteric site is difficult, as conformations required for receptor activation are poorly understood. Guided by photopharmacology, a set of prearranged positive allosteric modulators (PAMs) with restricted degrees of freedom was designed and tested against the glucagon-like peptide-1 receptor (GLP-1R), a GPCR involved in glucose homeostasis. Compounds incorporating a trans-stilbene comprehensively outperformed those with a cis-stilbene, as well as the benchmark BETP, as GLP-1R PAMs. We also identified major effects of ligand conformation on GLP-1R binding kinetics and signal bias. Thus, we describe a photopharmacology-directed approach for rational drug design, and introduce a new class of stilbene-containing PAM for the specific regulation of GPCR activity.