Selective Labeling of Living Cells by a Photo-Triggered Click Reaction

2009/10/08 by Andrei Poloukhtine, Andrei A. Poloukhtine, Ngalle Eric Mbua +4 · 410 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · #Acetylene #Advanced Biosensing Techniques and Applications #Advanced biosensing and bioanalysis techniques #Azide #Biochemistry #Biotin #Catalysis #Chemistry #Click Chemistry and Applications #Click chemistry #Combinatorial chemistry #Cycloaddition #Enone #Masking (illustration) #Organic chemistry #Photochemistry #Sialic acid

paper · doi:10.1021/ja9054096

published in Journal of the American Chemical Society 131(43), 15769-15776 (American Chemical Society)

openalex publication_date 2009/10/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Phototriggering of the metal-free azide to acetylene cycloaddition reaction was achieved by masking the triple bond of dibenzocyclooctynes as cyclopropenone. Such masked cyclooctynes do not react with azides in the dark. Irradiation of cyclopropenones results in the efficient (Phi(355) = 0.33) and clean regeneration of the corresponding dibenzocyclooctynes, which then undergo facile catalyst-free cycloadditions with azides to give corresponding triazoles under ambient conditions. In situ light activation of a cyclopropenone linked to biotin made it possible to label living cells expressing glycoproteins containing N-azidoacetyl-sialic acid. The cyclopropenone-based phototriggered click chemistry offers exciting opportunities to label living organisms in a temporally and spatially controlled manner and may facilitate the preparation of microarrays.

Citations

• A Strain-Promoted [3 + 2] Azide−Alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems
• Tetrazine Ligation: Fast Bioconjugation Based on Inverse-Electron-Demand Diels−Alder Reactivity
• Activity-Based Protein Profiling in Vivo Using a Copper(I)-Catalyzed Azide-Alkyne [3 + 2] Cycloaddition

Cited by

• Multiphoton Activation of Photo-Strain-Promoted Azide Alkyne Cycloaddition “Click” Reagents Enables in Situ Labeling with Submicrometer Resolution
• Temporal Labeling of Nascent RNA Using Photoclick Chemistry in Live Cells
• Light-Triggered Click Chemistry
• Photoclick Chemistry: A Bright Idea
• Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications
• Photo‐induced and Rapid Labeling of Tetrazine‐Bearing Proteins via Cyclopropenone‐Caged Bicyclononynes
• Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry
• Bioconjugation in Materials Science
• Protein modification by strain-promoted alkyne-nitrone cycloaddition. [europepmc]
• A metabolic alkene reporter for spatiotemporally controlled imaging of newly synthesized proteins in Mammalian cells. [europepmc]
• Biocompatible copper(I) catalysts for in vivo imaging of glycans. [europepmc]
• Metal-free sequential [3 + 2]-dipolar cycloadditions using cyclooctynes and 1,3-dipoles of different reactivity. [europepmc]
• Design and synthesis of highly reactive dienophiles for the tetrazine-trans-cyclooctene ligation. [europepmc]
• Strain-promoted alkyne-azide cycloadditions (SPAAC) reveal new features of glycoconjugate biosynthesis. [europepmc]
• Increasing the efficacy of bioorthogonal click reactions for bioconjugation: a comparative study. [europepmc]
• Thymidine analogues for tracking DNA synthesis. [europepmc]
• Thiacycloalkynes for copper-free click chemistry. [europepmc]
• Imaging beyond the proteome. [europepmc]
• A fluorogenic probe for the catalyst-free detection of azide-tagged molecules. [europepmc]
• Realizing the Promise of Chemical Glycobiology. [europepmc]
• Glycans in pathogenic bacteria--potential for targeted covalent therapeutics and imaging agents. [europepmc]
• Design strategies for bioorthogonal smart probes. [europepmc]
• Photo-Triggered Click Chemistry for Biological Applications. [europepmc]
• CYP450 Enzymes Effect Oxygen-Dependent Reduction of Azide-Based Fluorogenic Dyes. [europepmc]
• Spatiotemporal hydrogel biomaterials for regenerative medicine. [europepmc]
• Constructing New Bioorthogonal Reagents and Reactions. [europepmc]
• Achieving Controlled Biomolecule-Biomaterial Conjugation. [europepmc]
• Photo-induced and Rapid Labeling of Tetrazine-Bearing Proteins via Cyclopropenone-Caged Bicyclononynes. [europepmc]
• Bioorthogonal Strategies for Engineering Extracellular Matrices. [europepmc]
• Light-Triggered Click Chemistry. [europepmc]
• Photoclick Chemistry: A Bright Idea. [europepmc]
• Enabling In Vivo Photocatalytic Activation of Rapid Bioorthogonal Chemistry by Repurposing Silicon-Rhodamine Fluorophores as Cytocompatible Far-Red Photocatalysts. [europepmc]
• Bioorthogonal chemistry. [europepmc]

Related

• Multiphoton Activation of Photo-Strain-Promoted Azide Alkyne Cycloaddition “Click” Reagents Enables in Situ Labeling with Submicrometer Resolution
• Photo‐induced and Rapid Labeling of Tetrazine‐Bearing Proteins via Cyclopropenone‐Caged Bicyclononynes
• A Strain-Promoted [3 + 2] Azide−Alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems
• Temporal Labeling of Nascent RNA Using Photoclick Chemistry in Live Cells
• Light-Triggered Click Chemistry