Small molecule chemical probes play increasingly important roles in proteomics especially in the study of functional proteomics. The use of small molecule labeled probe has made lots of disease related targets come under observation. It is a powerful tool in drug discovery and development.
However, the majority of small molecular labeled probe was carried out in vitro before the year 2003, and in many cases do not reflect the accurate information of protein. Cravatt et al from the U.S Scripps institute introduced “click” chemistry into the design of small molecular probe. This approach make it possible to respond the protein functional state of the living cells or animal tissues and find disease related target protein when study the proteomics. The chemical small molecular probe plays an increasingly important role in drug discovery as this technical maturity.
The small molecular probe is designed based on its parent compound, according to the preliminary structure-activity relationship. The probe should have appropriate molecular activity. The action mechanism of the probe should be consistent with the parent compound. There are two function ways between active compounds with the target: Some of the active compound containing reactive group can react with the target protein to form a covalent bound, therefor this combination is very stable, irreversible. Another kind of interaction between compound and target protein is through the van der Waals forces or ionic bounding which is unstable and reversible.