Chemically triggered crosslinking with bioorthogonal cyclopropenones

We report a proximity-driven crosslinking strategy featuring bioorthogonal cyclopropenones. These motifs react with phosphines to form electrophilic ketene-ylides. Such intermediates can be trapped by neighboring proteins to form covalent adducts. Successful crosslinking was achieved using a model s...

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Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2020-09, Vol.56 (74), p.1883-1886
Main Authors: Row, R. David, Nguyen, Sean S, Ferreira, Andrew J, Prescher, Jennifer A
Format: Article
Language:English
Subjects:
Adducts
Bacteria - chemistry
Bacteria - cytology
Biocompatible Materials - chemical synthesis
Biocompatible Materials - chemistry
Biomolecules
Cross-Linking Reagents - chemical synthesis
Cross-Linking Reagents - chemistry
Crosslinking
Cyclopropanes - chemistry
Models, Molecular
Molecular Structure
Phosphines
Phosphines - chemistry
Proteins
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Summary:We report a proximity-driven crosslinking strategy featuring bioorthogonal cyclopropenones. These motifs react with phosphines to form electrophilic ketene-ylides. Such intermediates can be trapped by neighboring proteins to form covalent adducts. Successful crosslinking was achieved using a model split reporter, and the rate of crosslinking could be tuned using different phosphine triggers. We further demonstrated that the reaction can be performed in cell lysate. Based on these features, we anticipate that cyclopropenones will enable unique studies of protein-protein and other biomolecule interactions. Bioorthogonal cyclopropenones can be chemically triggered to crosslink interacting biomolecules.
ISSN:1359-7345
1364-548X
DOI:10.1039/d0cc04600k