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

Warren G. Lewis; Luke G. Green; Flavio Grynszpan; Zoran Radić; Paul R. Carlier; Palmer Taylor; M. G. Finn; K. Barry Sharpless

doi:10.1002/1521-3773(20020315)41:6<1053::AID-ANIE1053>3.0.CO;2-4

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

Warren G. Lewis
, Luke G. Green
, Flavio Grynszpan
, Zoran Radić
, Paul R. Carlier
, Palmer Taylor
, M. G. Finn
, K. Barry Sharpless

Research output: Contribution to journal › Article › peer-review

806 Scopus citations

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.

Original language	English
Pages (from-to)	1053-1057
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	41
Issue number	6
DOIs	https://doi.org/10.1002/1521-3773(20020315)41:6<1053::AID-ANIE1053>3.0.CO;2-4
State	Published - 15 Mar 2002
Externally published	Yes

Keywords

Combinatorial chemistry
Cycloaddition
Heterocycles
Hydrolases
Inhibitors

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10.1002/1521-3773(20020315)41:6<1053::AID-ANIE1053>3.0.CO;2-4

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Lewis, W. G., Green, L. G., Grynszpan, F., Radić, Z., Carlier, P. R., Taylor, P., Finn, M. G., & Sharpless, K. B. (2002). Click chemistry in situ: Acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks. Angewandte Chemie - International Edition, 41(6), 1053-1057. https://doi.org/10.1002/1521-3773(20020315)41:6<1053::AID-ANIE1053>3.0.CO;2-4

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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.",

keywords = "Combinatorial chemistry, Cycloaddition, Heterocycles, Hydrolases, Inhibitors",

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Lewis, WG, Green, LG, Grynszpan, F, Radić, Z, Carlier, PR, Taylor, P, Finn, MG & Sharpless, KB 2002, 'Click chemistry in situ: Acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks', Angewandte Chemie - International Edition, vol. 41, no. 6, pp. 1053-1057. https://doi.org/10.1002/1521-3773(20020315)41:6<1053::AID-ANIE1053>3.0.CO;2-4

Click chemistry in situ: Acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks. / Lewis, Warren G.; Green, Luke G.; Grynszpan, Flavio et al.
In: Angewandte Chemie - International Edition, Vol. 41, No. 6, 15.03.2002, p. 1053-1057.

Research output: Contribution to journal › Article › peer-review

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AU - Lewis, Warren G.

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AU - Radić, Zoran

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AU - Taylor, Palmer

AU - Finn, M. G.

AU - Sharpless, K. Barry

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N2 - 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.

AB - 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.

KW - Combinatorial chemistry

KW - Cycloaddition

KW - Heterocycles

KW - Hydrolases

KW - Inhibitors

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

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