On‐Bead Two‐Color (OBTC) Cell Screen for Direct Identification of Highly Selective Cell Surface Receptor Ligands

Combinatorial library screens can identify a suitable ligand for a biological target of interest out of thousands or even millions of compounds, and can play a key role in the drug development process. While conventional high‐throughput cell screens based on functional assays require expensive robotics, simple on‐bead combinatorial assays for ligand binding to the target protein can be done far more cheaply. This unit describes one such assay, developed using combinatorial peptoid libraries for targeting integral membrane receptors or other cell surface‐exposed molecules. In addition to the reduced cost, a unique advantage of this assay is the direct identification of the most selective ligands for a cell surface receptor that is expressed in its natural environment. Curr. Protoc. Chem. Biol . 4:35‐48 © 2012 by John Wiley & Sons, Inc.