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 pict...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2002-03, Vol.41 (6), p.1053-1057
Main Authors: Lewis, Warren G., Green, Luke G., Grynszpan, Flavio, Radić, Zoran, Carlier, Paul R., Taylor, Palmer, Finn, M. G., Sharpless, K. Barry
Format: Article
Language:English
Subjects:
Acetylcholinesterase - chemistry
Animals
Binding Sites
Cholinesterase Inhibitors - chemical synthesis
Cholinesterase Inhibitors - pharmacology
combinatorial chemistry
Combinatorial Chemistry Techniques - methods
cycloaddition
Drug Design
heterocycles
hydrolases
inhibitors
Kinetics
Mice
Torpedo
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Summary: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.
ISSN:1433-7851
1521-3773
DOI:10.1002/1521-3773(20020315)41:6<1053::AID-ANIE1053>3.0.CO;2-4