Novel GPR39 Agonsits: Correlation of Binding Affinity Using Label-Free Back-Scattering Interfreometry with Potency in Functional Assays.

Conformation-Sensitive, Back-Scattering Interferometry. Back Scattering Interferometry (BSI) is a truly label-free optical measurement technique that senses conformation-based changes upon ligand binding to a target. BSI is mass- and matrix-independent, enabling the technology to directly measure small molecule binding interactions with large, complex targets, integral membrane proteins, soluble protein targets and allosteric membrane and protein targets, all in native and native-like environments. The TruBind BSI System 100 is the world’s first free solution, label-free biosensor that detects changes in molecular conformation that arise from molecular aggregation, molecular binding, or molecular solvatic (hydration) effects. The TruBind BSI System 100 employs a simple optical train comprised of a coherent light source, a microfluidic interferometric channel and a CCD camera. The interaction of the laser with the sample fluid-filled channel results in a high-contrast interference fringe pattern. Fringe shift results from change in refractive index (RI) as molecular complexes form and alter target conformation. Assays employing discrete samples with constant target and titrated ligand concentrations allow compound affinity to be computed under equilibrium binding conditions.