Development of UV-responsive catch-and-release system of a cysteine protease model peptide

Cysteine proteases are attractive drug targets due to their involvement in a wide variety of diseases. To evaluate the potential of a particular protease as a drug target, use of a reagent that controls activity of the protease is indispensable. In this context, we have developed a catch-and-release reagent that first forms a covalent bond with the active center thiol of a cysteine protease to suppress its activity and then is removed by UV-irradiation to release the parent active protease. In this paper, the design and synthesis of a catch-and-release reagent of thiols are described. Its application to caging (catch) and UV-induced uncaging (release) of a model peptide derived from an active site of caspase-9 and introduction of a recognition moiety on the reagent are also reported.