Click Chemistry In Situ: Acetylcholinesterase as a Reaction Vessel for the Selective Assembly of a Femtomolar Inhibitor from an Array of Building Blocks

Abstract

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 missing content) should be directed to the corresponding author for the article.