Linear scaffolds for multivalent targeting of melanocortin receptors

Dilani Chathurika Dehigaspitiya, Bobbi L. Anglin, Kara R. Smith, Craig S. Weber, Ron Lynch, Eugene A Mash

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Molecules bearing one, two, three, or four copies of the tetrapeptide His-dPhe-Arg-Trp were attached to scaffolds based on ethylene glycol, glycerol, and d-mannitol by means of the copper-assisted azide-alkyne cyclization. The abilities of these compounds to block binding of a probe at the melanocortin 4 receptor were evaluated using a competitive binding assay. All of the multivalent molecules studied exhibited 30- to 40-fold higher apparent affinites when compared to a monovalent control. These results are consistent with divalent binding to receptor dimers. No evidence for tri- or tetravalent binding was obtained. Differences in the interligand spacing required for divalent binding, as opposed to tri- or tetravalent binding, may be responsible for these results.

Original languageEnglish (US)
Pages (from-to)11507-11517
Number of pages11
JournalOrganic and Biomolecular Chemistry
Volume13
Issue number47
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

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