Letters

Boronic Acid for the Traceless Delivery of Proteins into Cells

Graduate Program in Molecular and Cellular Pharmacology, University of Wisconsin—Madison, 1300 University Avenue, Madison, Wisconsin 53706, United States
Department of Chemistry, University of Wisconsin—Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States
§ Graduate Program in Cellular and Molecular Biology, University of Wisconsin—Madison, 1525 Linden Drive, Madison, Wisconsin 53706, United States
Department of Biochemistry, University of Wisconsin—Madison, 433 Babcock Drive, Madison, Wisconsin 53706, United States
ACS Chem. Biol., 2016, 11 (2), pp 319–323
DOI: 10.1021/acschembio.5b00966
Publication Date (Web): December 2, 2015
Copyright © 2015 American Chemical Society

Abstract

Abstract Image

The use of exogenous proteins as intracellular probes and therapeutic agents is in its infancy. A major hurdle has been the delivery of native proteins to an intracellular site of action. Herein, we report on a compact delivery vehicle that employs the intrinsic affinity of boronic acids for the carbohydrates that coat the surface of mammalian cells. In the vehicle, benzoxaborole is linked to protein amino groups via a “trimethyl lock.” Immolation of this linker is triggered by cellular esterases, releasing native protein. Efficacy is demonstrated by enhanced delivery of green fluorescent protein and a cytotoxic ribonuclease into mammalian cells. This versatile strategy provides new opportunities in chemical biology and pharmacology.

Supporting Information


The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acschembio.5b00966.

  • Procedures for the synthesis of B-TML-NHS ester and Ac-TML-NHS ester, their use in protein modification, analyses of cellular internalization, and Figures S1–S6 (PDF)

Citation data is made available by participants in CrossRef's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search in SciFinder.

Metrics

Article Views: 2,794 Times
Received 1 August 2015
Date accepted 2 December 2015
Published online 2 December 2015
Published in print 19 February 2016
Learn more about these metrics Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.
+
More Article Metrics
Explore by: