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. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z18552_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than…