biostudies-literatureQian KSwiss National Science FoundationFoundation for the National Institutes of HealthNIGMS NIH HHSe202419147https://www.ebi.ac.uk/biostudies/studies/S-EPMC11891630biostudies-literatureUnknown64(11)Protein poly- and oligophosphorylation are recently discovered post-translational modifications that remain poorly characterized due to (1) the difficulty of extracting endogenously polyphosphorylated species without degradation and (2) the absence of synthetic and analytical tools to prepare and characterize poly- and oligophosphorylated species in biochemical contexts. Herein, we report a methodology for the selective oligophosphorylation of peptides with monodisperse phosphate chain lengths (P_n=3-6). A library of oligophosphorimidazolide (oligoP-imidazolide) reagents featuring benzyl and o-nitrophenylethyl protecting groups was synthesized in moderate-to-good yields (65-93 %). These oligoP-imidazolide reagents enabled the selective and simultaneous conjugation of multiple phoAngewandte Chemie (International ed. in English)Monodisperse Chemical Oligophosphorylation of Peptides via Protected Oligophosphorimidazolide Reagents.PMC11891630R01GM130936CRSII5_209412R01 GM130936209412Hanf BFiedler DCummins CQian KfalseMonodisperse Chemical Oligophosphorylation of Peptides via Protected Oligophosphorimidazolide Reagents.Protein poly- and oligophosphorylation are recently discovered post-translational modifications that remain poorly characterized due to (1) the difficulty of extracting endogenously polyphosphorylated species without degradation and (2) the absence of synthetic and analytical tools to prepare and characterize poly- and oligophosphorylated species in biochemical contexts. Herein, we report a methodology for the selective oligophosphorylation of peptides with monodisperse phosphate chain lengths (P_n=3-6). A library of oligophosphorimidazolide (oligoP-imidazolide) reagents featuring benzyl and o-nitrophenylethyl protecting groups was synthesized in moderate-to-good yields (65-93 %). These oligoP-imidazolide reagents enabled the selective and simultaneous conjugation of multiple pho2025-01-01T00:00:00Z2025 Mar2025-04-04T08:22:37.759Z2025-04-04T08:22:37.759ZS-EPMC118916303962582910.1002/anie.202419147