Preparation of photo-cross-linked small molecule affinity matrices for affinity selection of protein targets for biologically active small molecules

Small molecule-immobilized affinity matrices are indispensable tools in chemical genomics to screen and purify protein targets for biologically active small molecules. Usually, prior to immobilization, small-molecules have to be derivatized at a position that does not significantly abrogate the intrinsic biological activity, or chemically synthesized to have an appropriate functional group for the immobilization chemistry. Here, we describe a photo-cross-linking technique to immobilize biologically active small molecules for protein target screening, without the need for chemical derivatization.