@article{55573d7f5d174d388436b9850a1db71d,
title = "Direct Intracellular Delivery of Benzene Diazonium Ions As Observed by Increased Tyrosine Phosphorylation",
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.",
author = "Cornejo, {Natasha R.} and Bismark Amofah and Austin Lipinski and Langlais, {Paul R.} and Indraneel Ghosh and Jewett, {John C.}",
note = "Funding Information: We thank former group members Dr. Abigail Shepard and Dr. Lindsay Guzm{\'a}n and current member Anjalee Wijetunge for early conversations regarding synthesis of these molecules. This work was supported in part by the NSF-CAREER award, given to J.C.J. (CHE-1552568), and an NIH award (R01GM115595) to I.G. This work was also supported in part by a grant to the University of Arizona from the Howard Hughes Medical Institute through the James H. Gilliam Fellowship for Advanced Study program (GT11435) to N.R.C. and J.C.J. All NMR data were collected in the NMR facility in the Department of Chemistry and Biochemistry at the University of Arizona. The purchase of the Bruker AVANCE III 400 MHz spectrometer was supported by the National Science Foundation under grant no. 840336 and the University of Arizona. All FTIR spectra were collected in the W.M. Keck Center for Nano-Scale Imaging in the Department of Chemistry and Biochemistry at the University of Arizona. This instrument was supported by Arizona Technology and Research Initiative Fund (A.R.S. 15-1648). We thank Yelena Feinstein and Kristen Keck at the University of Arizona Analytical & Biological Mass Spectrometry Facility for help with the MS analysis. Publisher Copyright: {\textcopyright} 2022 American Chemical Society.",
year = "2022",
month = apr,
day = "19",
doi = "10.1021/acs.biochem.1c00820",
language = "English (US)",
volume = "61",
pages = "656--664",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "8",
}