title: Multimeric alpha-MSH has increased efficacy to activate the melanocortin MC4 receptor.
abstract: alpha-Melanocyte stimulating hormone (alpha-MSH) has a relatively low affinity for the melanocortin MC4 receptor. Constructs of multimeric alpha-MSH varying from one to eight subunits were synthesized to test whether they displayed an improved ability to bind to and activate the human melanocortin MC4 receptor. alpha-MSH subunits were coupled by a flexible linker and placed in front of an IRES-eGFP sequence. Efficacy for activation of the melanocortin MC4 receptor increased with every extra subunit, resulting in a 100 fold lower EC50 value of alpha-MSH8 when compared with alpha-MSH1. Furthermore, supernatant of cells transfected with alpha-MSH8 proved to have an increased affinity to the melanocortin MC4 receptor when compared to cells transfected with the other multimers. Together, these data show that multimeric alpha-MSH has improved ability to activate the human melanocortin MC4 receptor in vitro.
authors: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, The Netherlands.
authors: Birgitte
authors: B
authors: Tiesjema
authors: Myrte
authors: M
authors: Merkestein
authors: Keith M
authors: KM
authors: Garner
authors: Mariken
authors: M
authors: de Krom
authors: Roger A H
authors: RA
authors: Adan
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists*; D014162:Transfection; D000521:alpha-MSH / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics
chemical_list: D008024:Ligands; D044105:Receptor, Melanocortin, Type 4; D000521:alpha-MSH