The ββα fold of zinc finger proteins as a “natural” protecting group. Chemoselective synthesis of a DNA-binding zinc finger derivative

We report the selective modification of cysteine residues engineered in peptides that have two additional cysteine residues as part of a Cys₂His₂ zinc finger motif. The chemoselective modification is achieved, thanks to the protecting effect exerted by the zinc cation upon coordination with the native cysteines and histidines of the zinc-finger fold. The strategy allows a straightforward synthesis of DNA binding zinc finger constructs.