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

Abstract

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.

Keywords

• protecting groups
• pKa values
• phenols
• mechanisms
• chemistry
• prodrug