title: Detection of regions in the MC1 receptor of importance for the selectivity of the MC1 receptor super-selective MS04/MS05 peptides.
abstract: We have investigated the ability of our earlier identified MS04-MS05 MSH-peptide analogues to bind to chimeric MC1-MC3 receptors. While the MS04 and MS05 peptides bind with nanomolar and sub-nanomolar affinities to the wild type MC1 receptor, they bind only with micromolar affinities for the wild type MC3 receptor, thus being the hitherto most MC1 receptor selective ligands. Upon exchanging portions involving transmembrane regions TM1, TM2-3, and TM6-7 of the MC1 receptor with corresponding portions of the MC3 receptor both of these peptides showed major losses of affinities. By contrast exchanges involving TM4-5 did not appreciably affect the affinity of either MS04 or MS05. Our data suggest that the binding pocket for the MS04-MS05 MSH-peptides is located between TM1-3 and TM6-7 of the melanocortin receptors.
authors.affiliation: Department of Pharmaceutical Pharmacology, Box 591, BMC, Uppsala University, SE-751 24, Uppsala, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Muceniece
authors.forename: I
authors.initials: I
authors.lastname: Mutule
authors.forename: F
authors.initials: F
authors.lastname: Mutulis
authors.forename: P
authors.initials: P
authors.lastname: Prusis
authors.forename: M
authors.initials: M
authors.lastname: Szardenings
authors.forename: J E
authors.initials: JE
authors.lastname: Wikberg
mesh_terms: D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011869:Radioligand Assay; D018043:Receptors, Corticotropin / Q000737:chemistry* / Q000378:metabolism; D044101:Receptors, Melanocortin
chemical_list: D010455:Peptides; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin