Multimeric alpha-MSH has increased efficacy to activate the melanocortin MC4 receptor.
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.
Tiesjema
Birgitte
B
Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, The Netherlands.
Merkestein
Myrte
M
Garner
Keith M
KM
de Krom
Mariken
M
Adan
Roger A H
RA
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
D008024:Ligands; D044105:Receptor, Melanocortin, Type 4; D000521:alpha-MSH