7] Caged peptides and proteins by targeted chemical modification

Abstract

Publisher Summary This chapter describes caged peptides and proteins such as 2-nitrobenzyl derivatives that are irreversibly activated on irradiation. A degree of reversible control of enzyme activity can be provided by the introduction of photoisomerizable groups into proteins. Two major considerations have dictated the choice of sulfhydryl-directed 2-nitrobenzyl reagents for derivatizing peptides and proteins. First is the ability to obtain a high yield of caged product. The possibility of carrying out the caging reaction in aqueous solution is especially important for proteins. Second, the caged reagent should be efficiently photolyzed at wavelengths that do not damage biological molecules. The chapter also describes two related approaches for caging peptides and proteins. They are the attachment of photocleavable protecting groups to the sulfur atoms of (1) cysteinyl residues or (2) thiophosphoryl groups. In general, the chemistry has been evaluated with small peptides and then extended to proteins. Nevertheless, it is stressed that caged peptides are themselves potentially useful reagents.