Intracellular Reactions Promoted by Bis(histidine) Miniproteins Stapled Using Palladium(II) Complexes
Angew. Chem. Int. Ed. 2020, 59, 9149-9154, 10.1002/anie.202002032
The generation of catalytically active metalloproteins inside living mammalian cells is a major research challenge at the interface between catalysis and cell biology. Herein we demonstrate that basic domains of bZIP transcription factors, mutated to include two histidine residues at i and i+4 positions, react with palladium(II) sources to generate catalytically active, stapled pallado-miniproteins. The resulting constrained peptides are efficiently internalized into living mammalian cells, where they perform palladium-promoted depropargylation reactions without cellular fixation. Control experiments confirm the requirement of the peptide scaffolding and the palladium staple for attaining the intracellular reactivity.
Metal: PdLigand type: Amino acidHost protein: GCN4 bZIP transcription factor (brHis2)Anchoring strategy: DativeOptimization: GeneticReaction: DepropargylationMax TON: ---ee: ---PDB: ---Notes: Whole cell catalysis