Accelerating Strain-Promoted Azide–Alkyne Cycloaddition Using Micellar Catalysis

Bioorthogonal conjugation reactions such as strain-promoted azide–alkyne cycloaddition (SPAAC) have become increasingly popular in recent years, as they enable site-specific labeling of complex biomolecules. However, despite a number of improvements to cyclooctyne design, reaction rates for SPAAC re...

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Bibliographic Details
Published in:Bioconjugate chemistry 2015-08, Vol.26 (8), p.1687-1691
Main Authors: Anderton, Grant I, Bangerter, Alyssa S, Davis, Tyson C, Feng, Zhiyuan, Furtak, Aric J, Larsen, Jared O, Scroggin, Triniti L, Heemstra, Jennifer M
Format: Article
Language:English
Subjects:
Alkynes - chemistry
Azides - chemistry
Catalysis
Click Chemistry
Copper - chemistry
Cycloaddition Reaction
Hydrophobic surfaces
Micelles
Organic chemistry
Surfactants
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Summary:Bioorthogonal conjugation reactions such as strain-promoted azide–alkyne cycloaddition (SPAAC) have become increasingly popular in recent years, as they enable site-specific labeling of complex biomolecules. However, despite a number of improvements to cyclooctyne design, reaction rates for SPAAC remain significantly lower than those of the related copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction. Here we explore micellar catalysis as a means to increase reaction rate between a cyclooctyne and hydrophobic azide. We find that anionic and cationic surfactants provide the most efficient catalysis, with rate enhancements of up to 179-fold for reaction of benzyl azide with DIBAC cyclooctyne. Additionally, we find that the presence of surfactant can provide up to 51-fold selectivity for reaction with a hydrophobic over hydrophilic azide. A more modest, but still substantial, 11-fold rate enhancement is observed for micellar catalysis of the reaction between benzyl azide and a DIBAC-functionalized DNA sequence, demonstrating that micellar catalysis can be successfully applied to hydrophilic biomolecules. Together, these results demonstrate that micellar catalysis can provide higher conjugation yields in reduced time when using hydrophobic SPAAC reagents.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.5b00274