Structure-based design, synthesis, and pharmacologic evaluation of peptide RGS4 inhibitors

J Pept Res. 2004 Feb;63(2):141-6. doi: 10.1111/j.1399-3011.2003.00114.x.


Regulators of G-protein signaling (RGS) proteins form a multifunctional signaling family. A key role of RGS proteins is binding to the G-protein Galpha-subunit and acting as GTPase-activating proteins (GAPs), thereby rapidly terminating G protein-coupled receptor (GPCR) signaling. Using the published RGS4-Gialpha1 X-ray structure we have designed and synthesized a series of cyclic peptides, modeled on the Gialpha Switch I region, that inhibit RGS4 GAP activity. These compounds should prove useful for elucidating RGS-mediated activity and serve as a starting point for the development of a novel class of therapeutic agent.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • GTPase-Activating Proteins / metabolism
  • Inhibitory Concentration 50
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / pharmacology*
  • RGS Proteins / antagonists & inhibitors*
  • RGS Proteins / metabolism
  • Structure-Activity Relationship


  • GTPase-Activating Proteins
  • Peptides, Cyclic
  • RGS Proteins
  • RGS4 protein