Click chemistry in situ: Acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks

Form-fitting chemistry in a protein mold is enabled by the use of the 1,3-dipolar cycloaddition of azides and alkynes. The enzyme acetylcholinesterase preferentially assembles one pair of these reactants, each of which bears a group that binds to adjacent positions on the protein structure (see picture), into a 1,2,3-triazole adduct that is the most potent noncovalent inhibitor of the enzyme yet developed.