Live-Cell Targeting of His-Tagged Proteins by Multivalent N-Nitrilotriacetic Acid Carrier Complexes

Selective and fast labeling of proteins in living cells is a major challenge. Live-cell labeling techniques require high specificity, high labeling density, and cell permeability of the tagging molecule to target the protein of interest. Here we report on the site-specific, rapid, and efficient labeling of endogenous and recombinant histidine-tagged proteins in distinct subcellular compartments using cell-penetrating multivalent chelator carrier complexes. In vivo labeling was followed in real time in living cells, demonstrating a high specificity and high degree of colocalization in the crowded cellular environment.