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 Citations (Scopus)

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

Fingerprint

Melanocortin Receptors
Receptor, Melanocortin, Type 4
Competitive Binding
Alkynes
Azides
Ethylene Glycol
Mannitol
Cyclization
Scaffolds
Glycerol
Copper
Bearings (structural)
Molecules
Dimers
Assays
mannitol
alkynes
glycerols
glycols
molecules

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

Cite this

Linear scaffolds for multivalent targeting of melanocortin receptors. / Dehigaspitiya, Dilani Chathurika; Anglin, Bobbi L.; Smith, Kara R.; Weber, Craig S.; Lynch, Ron; Mash, Eugene A.

In: Organic and Biomolecular Chemistry, Vol. 13, No. 47, 2015, p. 11507-11517.

Research output: Contribution to journalArticle

Dehigaspitiya, Dilani Chathurika ; Anglin, Bobbi L. ; Smith, Kara R. ; Weber, Craig S. ; Lynch, Ron ; Mash, Eugene A. / Linear scaffolds for multivalent targeting of melanocortin receptors. In: Organic and Biomolecular Chemistry. 2015 ; Vol. 13, No. 47. pp. 11507-11517.
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