Cytosolic Delivery of Proteins by Bioreversible Esterification
Name
Cytosolic delivery with SI.pdf
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1.83 MB
Format
Adobe PDF
Checksum (MD5)
594ae7910a97ae17bc1501f044783722
Author(s)
Lomax, Jo E.
Mix, Kalie
Raines, Ronald T
Date Issued
October 2017
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Citation
Mix, Kalie A., et al. “Cytosolic Delivery of Proteins by Bioreversible Esterification.” Journal of the American Chemical Society, vol. 139, no. 41, Oct. 2017, pp. 14396–98
Version
Author's final manuscript
Abstract
Cloaking its carboxyl groups with a hydrophobic moiety is shown to enable a protein to enter the cytosol of a mammalian cell. Diazo compounds derived from (p-methylphenyl)glycine were screened for the ability to esterify the green fluorescent protein (GFP) in an aqueous environment. Esterification of GFP with 2-diazo-2-(p-methylphenyl)-N,N-dimethylacetamide was efficient. The esterified protein entered the cytosol by traversing the plasma membrane directly, like a small-molecule prodrug. As with prodrugs, the nascent esters are substrates for endogenous esterases, which regenerate native protein. Thus, esterification could provide a general means to deliver native proteins to the cytosol.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1021/jacs.7b06597
