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

• Published in: Chembiochem : a European journal of chemical biology Vol. 18; no. 12; pp. 1117 - 1122
• Main Authors: Elnegaard, Rasmus L. B., Møllegaard, Niels Erik, Zhang, Qiang, Kjeldsen, Frank, Jørgensen, Thomas J. D.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 19.06.2017; John Wiley and Sons Inc
• Subjects: Affinity; alpha-amidation; Amides - chemistry; Amino Acid Sequence; Assaying; Backbone; Carboxypeptidases - chemistry; Casein; Caseins - chemistry; Caseins - radiation effects; Cations, Divalent; Chemistry; Enzyme Assays; Green Chemistry Technology; Irradiation; Mass spectrometry; Mass spectroscopy; Peptides; Pharmaceutical industry; phosphopeptides; Phosphopeptides - chemistry; Phosphopeptides - radiation effects; photocatalysis; Photolysis; Protein Binding; Tandem Mass Spectrometry; Ultraviolet radiation; Ultraviolet Rays; Uranium; Uranium Compounds - chemistry; uranyl; mass spectrometry; phosphopeptides; photocatalysis; uranyl; alpha-amidation
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201700103

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. Show me your photocleavage: The uranyl ion (UO22+) binds phosphopeptides with high affinity, and when irradiated with UV, it can cleave the peptide backbone. High‐accuracy MS of the photocleavage products showed that the primary products are C‐terminally amidated. This could be of pharmaceutical interest, as peptide amidation is a challenge in green pharmaceutical chemistry.