Single-site labeling of histidine in proteins, on-demand reversibility, and traceless metal-free protein purification.

A precision methodology distinguishes one His from all the nucleophilic residues and its multiple copies. An easy-to-operate C-N bond formation labels diverse proteins without adversely affecting their structure and function. The late-stage transformation allows installation of distinct probes. The chemically triggered reversibility enables traceless metal-free purification of proteins with a His-tag.