Templated alkylation of hexahistidine with Baylis–Hillman esters

Abstract

Alkylation of one of the imidazole rings of hexahistidine with Baylis–Hillman esters tethered to nitrilotriacetate residue was achieved in aqueous solutions at neutral pH and at micromolar concentrations in the presence of Ni²⁺, Cu²⁺, or Zn²⁺ cations. The utility of the approach for selective functionalization of His-tagged recombinant proteins was demonstrated by attachment of a fluorescent label to recombinant protein A with an alkynyl group followed by a “click” 1,3-dipolar cycloaddition reaction.