Chimaeric G alpha proteins: their potential use in drug discovery

Trends Pharmacol Sci. 1999 Mar;20(3):118-24. doi: 10.1016/s0165-6147(99)01320-6.


Approaches that allow ligand occupancy of a wide range of G protein-coupled receptors to be converted into robust assays amenable to relatively high-throughput analysis are ideal for screening for novel ligands at this class of receptor. Many attempts have been made to design universal ligand-screening systems such that any GPCR can be screened using a common assay end-point. Manipulation of the G protein within the assay system offers the possibility of achieving this. To better understand the domains involved in the interactions between G protein-coupled receptors, G proteins and effector polypeptides and the fine details of these contacts, a wide range of chimaeric G protein alpha subunits have been produced. Graeme Milligan and Stephen Rees discuss the information generated by such studies and the ways in which such chimaeric G proteins can be integrated into assay systems for drug discovery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Drug Evaluation, Preclinical / methods
  • GTP-Binding Proteins / therapeutic use*
  • Recombinant Fusion Proteins / therapeutic use*
  • Technology, Pharmaceutical*


  • Recombinant Fusion Proteins
  • GTP-Binding Proteins