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

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

  • Bioorg Med Chem Lett. 2011 May 15;21(10):3099-102. doi: 10.1016/j.bmcl.2011.03.019.
Alexander V Mayorov 1,  Minying Cai,  Erin S Palmer,  Dustin K Tanaka,  James P Cain,  Matthew M Dedek,  Bahar Tan,  Dev Trivedi,  Victor J Hruby
Affiliations

Affiliation

  • 1 Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
PMID: 21486697 DOI: 10.1016/j.bmcl.2011.03.019
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.

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