Author/Authors :
Darren A. Thompson، نويسنده , , Biaoxin Chai، نويسنده , , Hilary L. E. Rood، نويسنده , , Michael A. Siani، نويسنده , , Nicholai R. Douglas، نويسنده , , Ira Gantz، نويسنده , , Glenn L. Millhauser، نويسنده ,
Abstract :
The Agouti Related Protein (AGRP) is an endogenous antagonist of melanocortin-3 and -4 receptors, each of which plays a key role in body weight homeostasis. We designed a peptoid trimer based on AGRP 111–113 in which a single chiral atom is used to partially restrain the backbone structure. Peptoid 5 displaced both radiolabeled Nle4-α-MSH (IC50=3.1 μM) and AGRP (86–132) (IC50=1.9 μM) from the human melanocortin-4 receptor and functioned as an antagonist of α-MSH stimulated cAMP generation, thus providing an important lead in the development of AGRP mimetics.
