Effect of detergent on "promiscuous" inhibitors.
The term "promiscuous" inhibitors has been coined for compounds whose inhibition mechanism involves the interaction of aggregates of many compound molecules with the target protein, rather than the binding of individual molecules. This paper demonstrates that promiscuous inhibitors can be differentiated from classical 1:1 inhibitors by the judicious use of detergents, making it possible to configure assays that significantly reduce this undesirable mechanism of inhibition without compromising assay performance.
Ryan
Ali J
AJ
Computational and Structural Sciences, GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Gray
Norman M
NM
Lowe
Peter N
PN
Chung
Chun-wa
CW
D000098:Acetophenones / Q000737:chemistry; D000667:Ampicillin / Q000737:chemistry; D001578:Benzopyrans / Q000737:chemistry; D001897:Boronic Acids / Q000737:chemistry; D002384:Catalysis; D003224:Congo Red / Q000737:chemistry; D003902:Detergents / Q000737:chemistry*; D016972:Enterobacter cloacae / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry; D013876:Thiophenes / Q000737:chemistry; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry
C476591:3-((2-thienyl)thiophenyliden-2-yl)-2H-indol-2-one; D000098:Acetophenones; D001578:Benzopyrans; D001897:Boronic Acids; D003902:Detergents; D004791:Enzyme Inhibitors; D007211:Indoles; D013876:Thiophenes; D065093:beta-Lactamase Inhibitors; C476590:thianaphthene-2-boronic acid; D003224:Congo Red; D000667:Ampicillin; C085746:rottlerin; D001618:beta-Lactamases