Chimaeric G alpha proteins: their potential use in drug discovery.
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.
Milligan
G
G
University of Glasgow, UK.
Rees
S
S
D004353:Drug Evaluation, Preclinical / Q000379:methods; D019204:GTP-Binding Proteins / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D013678:Technology, Pharmaceutical
D011993:Recombinant Fusion Proteins; D019204:GTP-Binding Proteins