Synthesis and characterization of a Eu-DTPA-PEGO-MSH(4) derivative for evaluation of binding of multivalent molecules to melanocortin receptors

Liping Xu, Josef Vagner, Ramesh Alleti, Venkataramanarao Rao, Bhumasamudram Jagadish, David L. Morse, Victor J. Hruby, Robert J. Gillies, Eugene A. Mash

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2489-2492
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number8
DOIs
StatePublished - Apr 15 2010

Keywords

  • Human melanocortin 4 receptor
  • MSH(4)
  • Multimeric ligands
  • NDP-α-MSH

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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