Azaphilone Probe Maps Reactive Lysines Across Live Bacterial Proteomes
- SCL-alkyne, a simplified azaphilone derived from the natural product sclerotiorin, was designed to profile lysine reactivity proteome-wide in bacteria.
- It was highly lysine-selective in vitro and in live E. coli; most engaged sites were lysines or protein N-termini, and only a small subset of reactive lysines sat in functional regions.
- Enrichment analysis pointed to bacterial chemotaxis as a major target pathway, which was then confirmed.
💡 Points
Covalent ligand discovery has been cysteine-centric, and lysine-directed scaffolds beyond sulfonyl fluorides and activated esters are scarce, so a natural-product-derived option is appealing. The observation that few reactive lysines are functional is a sober reminder that reactivity is cheap and function is not. As an E. coli preprint it is a starting point for covalent fragments, not a lead.