(418e) Magnetic Screening Nanoplatform with Immobilized Transmembrane Receptors for Drug Discovery

The current drug discovery process mainly focus high throughput screening (HTS), which requires analyzing each compound, labor-intensive and costly. In particular, effective HTS approaches using transmembrane protein receptors as screening targets for direct compound identification are limited. The use of transmembrane targets is important because over 60% of modern pharmaceuticals use membrane proteins as prime targets. In contrast, the immobilized proteins for magnetic bead technology are limited to purified cytosolic protein (enzymes or antibodies), which is not applicable to transmembrane proteins that require boundary lipids to function. In this presentation, we will discuss a newly developed magnetic screening nanoplatform (MSN) based on cell-membrane coated magnetic nanoparticles with immobilized receptors within membrane for drug discovery. The immobilized transmembrane receptors can directly identify binding compounds through specific ligand-receptor interactions, as a screening funnel to quickly narrow down a large number of molecules to compounds of binding, while magnetic nanoparticles inside enable rapid binder isolation. Here, we will use receptor tropomyosin-receptor-kinase B and voltage-gated sodium ion channels to demonstrate the feasibility and applicability of this screening platform. Specifically, we will discuss the development of the platform, screening process, and compound using different screening sources. Most importantly, our preliminary biological tests indicated the potential activities of the identified compounds.