Direct Intracellular Delivery of Benzene Diazonium Ions As Observed by Increased Tyrosine Phosphorylation

Natasha R. Cornejo, Bismark Amofah, Austin Lipinski, Paul R. Langlais, Indraneel Ghosh, John C. Jewett

Research output: Contribution to journalArticlepeer-review

Abstract

A challenge within the field of bioconjugation is developing probes to uncover novel information on proteins and other biomolecules. Intracellular delivery of these probes offers the promise of giving relevant context to this information, and these probes can serve as hypothesis-generating tools within complex systems. Leveraging the utility of triazabutadiene chemistry, herein, we discuss the development of a probe that undergoes reduction-mediated deprotection to rapidly deliver a benzene diazonium ion (BDI) into cells. The intracellular BDI resulted in an increase in global tyrosine phosphorylation levels. Seeing phosphatase dysregulation as a potential source of this increase, a tyrosine phosphatase (PTP1B) was tested and shown to be both inhibited and covalently modified by the BDI. In addition to the expected azobenzene formation at tyrosine side chains, key reactive histidine residues were also modified.

Original languageEnglish (US)
Pages (from-to)656-664
Number of pages9
JournalBiochemistry
Volume61
Issue number8
DOIs
StatePublished - Apr 19 2022
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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