Superfast Tetrazole–BCN Cycloaddition Reaction for Bioorthogonal Protein Labeling on Live Cells

Here we report the design of a superfast bioorthogonal ligation reactant pair comprising a sterically shielded, sulfonated tetrazole and bicyclo[6.1.0]­non-4-yn-9-ylmethanol (BCN). The design involves placing a pair of water-soluble N-sulfonylpyrrole substituents at the C-phenyl ring of diphenyltetr...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2022-01, Vol.144 (1), p.57-62
Main Authors: Kumar, Gangam Srikanth, Racioppi, Stefano, Zurek, Eva, Lin, Qing
Format: Article
Language:English
Subjects:
Bridged Bicyclo Compounds - chemistry
Cycloaddition Reaction
Humans
Molecular Structure
Tetrazoles - chemistry
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Summary:Here we report the design of a superfast bioorthogonal ligation reactant pair comprising a sterically shielded, sulfonated tetrazole and bicyclo[6.1.0]­non-4-yn-9-ylmethanol (BCN). The design involves placing a pair of water-soluble N-sulfonylpyrrole substituents at the C-phenyl ring of diphenyltetrazoles to favor the photoinduced cycloaddition reaction over the competing nucleophilic additions. First-principles computations provide vital insights into the origin of the tetrazole–BCN cycloaddition’s superior kinetics compared to the tetrazole–spirohexene cycloaddition. The tetrazole–BCN cycloaddition also enabled rapid bioorthogonal labeling of glucagon receptors on live cells in as little as 15 s.
ISSN:0002-7863
1520-5126
1520-5126
DOI:10.1021/jacs.1c10354