NMR Insights into the Structure-Function Relationships in the Binding of Melanocortin Analogues to the MC1R Receptor.

ABSTRACT: Linear and cyclic analogues of the α-melanocyte stimulating hormone (α-MSH) targeting the human melanocortin receptor 1 (MC1R) are of pharmacological interest for detecting and treating melanoma. The central sequence of α-MSH (His-Phe-Arg-Trp) has been identified as being essential for receptor binding. To deepen current knowledge on the molecular basis for α-MSH bioactivity, we aimed to understand the effect of cycle size on receptor binding. To that end, we synthesised two macrocyclic isomeric α-MSH analogues, c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys]-Lys-NH₂ (CycN-K6) and c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys-Lys]-NH₂ (CycN-K7). Their affinities to MC1R receptor were determined by competitive binding assays, and their structures were analysed by ¹H and ¹³C NMR. The

SUBMITTER: Morais M 

PROVIDER: S-EPMC6152105 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature