Abstract
A lipid-compatible, dual-functionalised, and enantio-specific chemical linker, with a diazirine-based photoactivatable warhead and bioorthogonal click handle, was achieved in an 8-step synthetic sequence in 6.5% overall yield. The synthesis commences with a cheap and commercially accessible alcohol, with the key step being a base-catalysed, sequential oxa-Michael addition before diazirine installation. This novel linker is expected to enable construction of new types of chemical probes with improved abilities for interrogating endogenous protein activities in native environments of the cell.
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