Chemical tools address the biology of proteins in the cellular environment where the protein is limiting but not absent and can probe and manipulate a protein’s function in a controlled manner. Such a molecular toolkit comprises ligands, labeled inhibitors, and solid-support immobilized inhibitors that are developed with a biological application in mind. For example these can be modulated to be cell permeable or impermeable, targeted to specific cellular compartments, or tailored to be useful for a specific investigation.
As research aids, chemical tools have the potential to extend the study of single targets to a particular class of molecules or even to an entire proteome. In addition, the development of powerful chemical tools designed to probe or modulate the activity of biomolecules in live biological systems can lay the foundation for a type of “live biochemistry and biology.” Such studies can complement traditional, genetic, biochemical, and biological approaches by aiding the molecular characterization of biomolecules both in vitro and within their natural biological contexts.
Together with medicinal chemistry, which provides the know-how to adjust these chemical tools to have the characteristics necessary for in vivo studies (i.e., favorable bioavailability and toxicology, proper in vivo target modulation), these two strategies promise to offer important insights into the function and regulation of the molecules that regulate life processes and, in turn, facilitate development of new therapeutics for the treatment of diseases.