Cell-membrane coated iron oxide nanoparticles for isolation and specific identification of drug leads from complex matrices. Issue 13 (19th March 2019)

• Record Type: Journal Article
• Authors: Sherwood, Jennifer; Sowell, Josiah; Beyer, Nicholas; Irvin, Jessica; Stephen, Cayman; Antone, Angelo J.; Bao, Yuping; Ciesla, Lukasz M.
• Is Part Of: Nanoscale. Volume 11:Issue 13(2019)
• Page Start: 6352
• Page End: 6359
• Publication Date: 2019-03-19
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/c9nr01292c
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : New drug discovery technique to identify compounds binding to transmembrane receptors in complex mixtures. Abstract : The lack of suitable tools for the identification of potential drug leads from complex matrices is a bottleneck in drug discovery. Here, we report a novel method to screen complex matrices for new drug leads targeting transmembrane receptors. Using α3 β4 nicotinic receptors as a model system, we successfully demonstrated the ability of this new tool for the specific identification and effective extraction of binding compounds from complex mixtures. The formation of cell-membrane coated nanoparticles was confirmed by transmission electron microscopy. In particular, we have developed a direct tool to evaluate the presence of functional α3 β4 nicotinic receptors on the cell membrane. The specific ligand binding to α3 β4 nicotinic receptors was examined through ligand fishing experiments and confirmed by high-performance liquid chromatography coupled with diode-array detection and electrospray ionization mass spectrometry. This tool has a great potential to transform the drug discovery process focusing on identification of compounds targeting transmembrane proteins, as more than 50% of all modern pharmaceuticals use membrane proteins as prime targets.