Novel targeting strategy based on multimeric ligands for drug delivery and molecular imaging: Homooligomers of α-MSH

Josef Vagner, Heather L. Handl, Robert J. Gillies, Victor J. Hruby

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Homooligomers constructed with 4- and 6-amino acid fragments of melanocortin (α-MSH) bind with higher affinity and with apparent cooperativity to melanocortin receptor, compared to their constituent monomers. Individual ligands were tethered with various spacers of different length and rigidity and the influence of spacers on binding was studied. Binding assays were performed on cells transfected with the melanocortin receptor, hMC4R. There is a 5-7-fold decrease in the EC50 with the addition of each subunit, going from monomer to trimer. The Hill coefficient increases from 0.76 for the monomer to 1.12 for the dimer and 1.35 for the trimer. These data show a general trend of increasing avidity with increasing number of ligands in oligomers.

Original languageEnglish (US)
Pages (from-to)211-215
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume14
Issue number1
DOIs
StatePublished - Jan 5 2004

ASJC Scopus subject areas

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

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