Synthesis and characterization of a Eu-DTPA-PEGO-MSH(4) derivative for evaluation of binding of multivalent molecules to melanocortin receptors |
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Authors: | Liping Xu Josef Vagner Ramesh Alleti Venkataramanarao Rao Bhumasamudram Jagadish David L Morse Victor J Hruby Robert J Gillies Eugene A Mash |
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Institution: | 1. H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA;2. The Bio5 Institute, University of Arizona, Tucson, AZ 85721-0240, USA;3. Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721-0041, USA |
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Abstract: | A labeled variant of MSH(4), a tetrapeptide that binds to the human melanocortin 4 receptor (hMC4R) with low μM affinity, was prepared by solid-phase synthesis methods, purified, and characterized. The labeled ligand, Eu-DTPA-PEGO-His-dPhe-Arg-Trp-NH2, exhibited a Kd for hMC4R of 9.1 ± 1.4 μM, approximately 10-fold lower affinity than the parental ligand. The labeled MSH(4) derivative was employed in a competitive binding assay to characterize the interactions of hMC4R with monovalent and divalent MSH(4) constructs derived from squalene. The results were compared with results from a similar assay that employed a more potent labeled ligand, Eu-DTPA-NDP-α-MSH. While results from the latter assay reflected only statistical effects, results from the former assay reflected a mixture of statistical, proximity, and/or cooperative binding effects. |
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