Photolysis of an Intrachain Peptide Disulfide Bond: Primary and Secondary Processes, Formation of H2S, and Hydrogen Transfer Reactions

The photodissociation of intrachain disulfide bonds in a model peptide and salmon calcitonin generates a series of cyclic peptide products following the generation of a CysS• thiyl radical pair. Key to the formation of these cyclic products are disproportionation and reversible hydrogen atom transfer reactions as well as secondary photoreactions, which lead to C−S bond breakage of primary photoproducts. Depending on the wavelength of the incident light, disulfides ultimately convert into cyclic thioethers. An important photolytic product is H2S, which is highly relevant for the production and storage of protein pharmaceuticals, where H2S can catalyze disulfide scrambling and protein degradation.