Uranyl Photocleavage of Phosphopeptides Yields Truncated C‐Terminally Amidated Peptide Products

The uranyl ion (UO₂²⁺) binds phosphopeptides with high affinity, and when irradiated with UV‐light, it can cleave the peptide backbone. In this study, high‐accuracy tandem mass spectrometry and enzymatic assays were used to characterise the photocleavage products resulting from the uranyl photocleavage reaction of a tetraphosphorylated β‐casein model peptide. We show that the primary photocleavage products of the uranyl‐catalysed reaction are C‐terminally amidated. This could be of great interest to the pharmaceutical industry, as efficient peptide amidation reactions are one of the top challenges in green pharmaceutical chemistry.