Abstract

Kinetic profiling of drug–target interactions using surface-based label-free technologies is well established for soluble pharmaceutical targets but is challenging to execute for membrane proteins and in particular for G-protein–coupled receptors (GPCRs). That is because surface immobilization of GPCRs tends to alter their configuration and function, leading to low target coverage and non-specific binding. InSingulo has developed a novel biosensing technology based on temporally resolved imaging of the binding of single liposomes, containing membrane protein targets, with surface-immobilized ligands in the presence of screened compounds (dynamic inhibition in solution assay or dISA). dISA assays enable measurements of interaction kinetics between compounds and membrane protein targets embedded in their native environment at the single molecule level. In this talk, focus will be on technical details of the dISA technology, the opportunities using it and examples of application for GPCR screening.