Synthesis and Receptor Binding Analysis of Thirteen Oligomeric α-MSH Analogs

Abstract

Thirteen oligomeric analogs from dimers up to a hexamer of α-melanocyte-stimulating hormone (α-MSH) were synthesized and tested on melanoma cells for their ability to bind to melanocortin type 1 (MC1) receptors and to stimulate melanin production in the cells. The peptidic oligomers were made by linking several copies of the α-MSH fragment analog Nle-Asp-His-[D-Phe]-Arg-Trp-Lys-NH₂ to different templates through formation of oxime bonds. They were found to have binding affinities at 37°C up to 8 times higher and melanogenesis-inducing activities up to 4 times higher than those of the native hormone. At 15°C, one dimer showed a binding affinity 20 times higher than that of α-MSH. These results are discussed in terms of possible bridging of neighboring receptors which has been suggested to occur in some other systems.