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Chemically triggered crosslinking with bioorthogonal cyclopropenones.

ABSTRACT: 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.

SUBMITTER: Row RD

PROVIDER: S-EPMC7501174 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Chemically triggered crosslinking with bioorthogonal cyclopropenones.

Row R David RD Nguyen Sean S SS Ferreira Andrew J AJ Prescher Jennifer A JA

Chemical communications (Cambridge, England) 20200901 74

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 an ...[more]

PMID: 32808608

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