Synthesis and biological activity of novel peptide mimetics as melanocortin receptor agonists

Bioorg Med Chem Lett. 2008 Feb 1;18(3):1223-8. doi: 10.1016/j.bmcl.2007.11.109. Epub 2007 Dec 4.

Abstract

A series of novel peptidomimetic analogs was prepared containing cyclohexyl, phenyl, or heterocyclic groups to ostensibly orient the guanidine or mimic of an arginine in a putative melanocortin receptor ligand pharmacophore. Some binding affinity at the melanocortin receptors MC(3) and MC(4) was noted. In silico docking also indicated that the relative positions of the hydrogen-bonding sites and hydrophobic regions of the compounds are reasonably well matched to the receptor-binding site. This may present a lead entry into a selective series of MC(4)R agonists.

MeSH terms

  • Arginine / chemistry
  • Guanidines / chemistry
  • Humans
  • Models, Biological
  • Molecular Mimicry
  • Molecular Structure
  • Peptides / chemistry*
  • Receptor, Melanocortin, Type 3 / agonists*
  • Receptor, Melanocortin, Type 4 / agonists*
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology

Substances

  • Guanidines
  • Peptides
  • Receptor, Melanocortin, Type 3
  • Receptor, Melanocortin, Type 4
  • Triazoles
  • Arginine