Small-molecule reagents for cellular pull-down experiments

Affinity purification of interacting proteins from cellular extracts is a powerful technique for identifying the cellular targets of small molecules. Affinity matrix-based small-molecule reagents are usually prepared by conjugating small molecules of interest to a solid support such as agarose. This protocol describes an efficient and robust method to immobilize small molecules containing a primary alcohol, a common functional group in small molecules, especially in small molecules prepared using diversity-oriented synthesis. This method comprises one element of a systematic approach to the target identification problem in chemical biology.