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Self-immolation (SI) is the key principle of ProTide nucleotide prodrugs such as remdesivir, which is currently used to treat COVID-19 patients. Developing novel tailor-made SI systems requires new analytical methods for the detection and monitoring of SI. We developed a robust method for SI analysis using novel phosphate-based SI linkers with NMR traceable cyclic intermediates to distinguish SI from alternative fragmentation pathways and to monitor cargo release in real time.

Phosphate linkers with traceable cyclic intermediates for self-immolation detection and monitoring