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

Abstract
Thirteen oligomeric analogs from dimers up to a hexamer of alpha-melanocyte-stimulating hormone (alpha-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 alpha-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 degrees C up to 8 times higher and melanogenesis-inducing activities up to 4 times higher than those of the native hormone. At 15 degrees C, one dimer showed a binding affinity 20 times higher than that of alpha-MSH. These results are discussed in terms of possible bridging of neighboring receptors which has been suggested to occur in some other systems.