title: Peptoid mimics of agouti related protein.
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-alpha-MSH (IC(50)=3.1 microM) and AGRP (86-132) (IC(50)=1.9 microM) from the human melanocortin-4 receptor and functioned as an antagonist of alpha-MSH stimulated cAMP generation, thus providing an important lead in the development of AGRP mimetics.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz 95064, USA. thompson@chemistry.ucsc.edu
authors.forename: Darren A
authors.initials: DA
authors.lastname: Thompson
authors.forename: Biao-Xin
authors.initials: BX
authors.lastname: Chai
authors.forename: Hilary L E
authors.initials: HL
authors.lastname: Rood
authors.forename: Michael A
authors.initials: MA
authors.lastname: Siani
authors.forename: Nicholai R
authors.initials: NR
authors.lastname: Douglas
authors.forename: Ira
authors.initials: I
authors.lastname: Gantz
authors.forename: Glenn L
authors.initials: GL
authors.lastname: Millhauser
mesh_terms: D054369:Agouti-Related Protein; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D034444:Peptoids / Q000737:chemistry* / Q000494:pharmacology; D011506:Proteins / Q000737:chemistry* / Q000502:physiology; D011869:Radioligand Assay; D044101:Receptors, Melanocortin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D000521:alpha-MSH / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: C515198:AGRP protein, human; D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D034444:Peptoids; D011506:Proteins; D044101:Receptors, Melanocortin; C430443:agouti-related protein (86-132), human; D000521:alpha-MSH; D000242:Cyclic AMP