Peptidomimetics of Arg-Phe-NH2 as small molecule agonists of Mas-related gene C (MrgC) receptors

Bioorg Med Chem. 2014 Nov 1;22(21):5831-7. doi: 10.1016/j.bmc.2014.09.025. Epub 2014 Sep 19.

Abstract

A series of Arg-Phe-NH2 peptidomimetics containing an Arg mimetic were synthesized and tested as agonists of human MrgX1, rat MrgC, and mouse MrgC11 receptors. As predicted from the previously established species specificity, these peptidomimetics were found to be devoid of MrgX1 agonist activity. In contrast, these compounds acted as agonists of MrgC and/or MrgC11 with varying degrees of potency. These new peptidomimetics should complement the existing small molecule human MrgX1 agonists and enhance our ability to assess the therapeutic utility of targeting Mrg receptors in rodent models.

Keywords: Agonist; Arginine mimetic; Mas-related gene (Mrg) receptors; Peptidomimetic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • HEK293 Cells
  • Humans
  • Mice
  • Neuropeptides / chemical synthesis
  • Neuropeptides / chemistry*
  • Neuropeptides / metabolism
  • Peptidomimetics / pharmacology
  • Protein Binding / drug effects
  • Rats
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / metabolism
  • Small Molecule Libraries / pharmacology
  • Transfection

Substances

  • MrgC11 protein, mouse
  • Mrgprc protein, rat
  • Neuropeptides
  • Peptidomimetics
  • Receptors, G-Protein-Coupled
  • Small Molecule Libraries
  • mas-related gene-X1 receptor, human
  • arginylphenylalaninamide