Cyclic lactam hybrid α-MSH/Agouti-related protein (AGRP) analogues with nanomolar range binding affinities at the human melanocortin receptors

Alexander V. Mayorov, Minying Cai, Erin S. Palmer, Dustin K. Tanaka, James P. Cain, Matthew M. Dedek, Bahar Tan, Dev Trivedi, Victor J. Hruby

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

A novel hybrid melanocortin pharmacophore was designed based on the topographical similarities between the pharmacophores of Agouti related protein (AGRP) an endogenous melanocortin antagonist, and α-melanocyte-stimulating hormone (α-MSH), an endogenous melanocortin agonist. When employed in two different 23-membered macrocyclic lactam peptide templates, the designed hybrid AGRP/MSH pharmacophore yielded non-competitive ligands with nanomolar range binding affinities. The topography-based pharmacophore hybridization strategy will prove useful in development of unique non-competitive melanocortin receptor modulators.

Original languageEnglish (US)
Pages (from-to)3099-3102
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number10
DOIs
StatePublished - May 15 2011

Keywords

  • Agouti-related protein
  • Human melanocortin receptors
  • Hybrid pharmacophore
  • Macrocyclic peptide
  • α-MSH

ASJC Scopus subject areas

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

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