Ago-Antagonists for G Protein-Coupled Peptide Hormone Receptor by Modifying the Agonist's Signalling Domain
Most of the pharmaceuticals today target at G protein-coupled receptors (GPCRs)  that transmit extracellular signals into cells. GPCRs are promiscuous, that means a single receptor can activate different signalling events, presumably via different G protein subtypes. Functional selectivity of GPCR ligands has been observed and points at a new orientation in pharmaceutical research. However, the structural characteristics of ligands that produce this selectivity are far from known .
The polypeptide hormone urocortin I (Ucn) activates both Gs and Gi proteins via the corticotropin-releasing factor receptor type 1 (CRF1). We have recently developed an easy method for the separate measurement of Gs and Gi activation at HEK 293 cells stably transfected with cDNA coding for CRF1 [3, 4]. The aim of this study was to search for structural determinants of the peptide agonist Ucn (DDPPLSIDLT FHLLRTLLEL ARTQSQRERA EQNRIIFDSV-NH2) that direct the signalling to Gs and Gi,...
KeywordsSingle Receptor Peptide Agonist Stimulate cAMP Production Bulky Amino Acid Peptide Hormone Receptor
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