The determination of the potential value of receptor trafficking at melanocortin receptors has been hampered by the absence of known biased ligands. Heterobivalent MC4R ligands linking agonist to anta Show more
The determination of the potential value of receptor trafficking at melanocortin receptors has been hampered by the absence of known biased ligands. Heterobivalent MC4R ligands linking agonist to antagonist small peptidic moieties were designed and found to act as Gιs enhancers while minimally activating β-arrestin recruitment. The strategy invoked offers intriguing promise as a surprising approach that is possibly broadly applicable to the challenge of designing biased ligands at other GPCRs. Show less