Photo-Cross-Linked Small-Molecule Affinity Matrix for Facilitating Forward and Reverse Chemical Genetics

摘要

Affinity purification of small-molecule binding protein has been one of the most important techniques in forward chemical genetics (Figure 1 a).[1], [2] Once hit compound(s) which induce a specific phenotype in a cellular system are identified, the next step is to identify the molecular target. Thus, derivatization of the small molecules and structure-activity relationship studies are conducted to prepare tagged probes (for example, biotin conjugates) that can be used in a pull-down assay. Many targets of biologically important drugs have been discovered or identified by using this technique.[3]-[6] However, it remains challenging and time-consuming to derivatize small molecules without a loss in biological activity, and an easy-to-use, universal approach would be of great benefit in this context.