Detecting protein-small molecule interactions using fluorous small-molecule microarrays.

General binding assays involving microarrays of small molecules can be used to identify small molecule ligands for nearly any protein, even in the absence of knowledge about protein structure or function. Several suitable methods for manufacturing small molecule microarrays (SMMs) exist and different immobilization methods may be more or less preferable for any given application. Here, we describe a protocol for noncovalent and homogenous capture of small molecules using fluorous interactions between small molecules containing fluorocarbon tags and fluorocarbon-coated glass surfaces. These arrays are especially useful for applications that require display of compounds in a specific orientation such as screening biased libraries.