Boronic Acid for the Traceless Delivery of Proteins into Cells

ACS Chem Biol. 2016 Feb 19;11(2):319-23. doi: 10.1021/acschembio.5b00966. Epub 2015 Dec 15.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Boronic Acids / chemistry*
  • Boronic Acids / metabolism
  • CHO Cells
  • Cell Line, Tumor
  • Cell Membrane Permeability
  • Cricetulus
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Green Fluorescent Proteins / administration & dosage*
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / pharmacokinetics
  • Humans
  • Models, Molecular
  • Ribonucleases / administration & dosage*
  • Ribonucleases / chemistry
  • Ribonucleases / pharmacokinetics

Substances

  • Boronic Acids
  • Drug Carriers
  • Green Fluorescent Proteins
  • Ribonucleases