Direct delivery of proteins into mammalian cells is a challenging problem in biological and biomedical applications. The most common strategies for the delivery of proteins into the cells include the use of cell-penetrating peptides or supercharged proteins. Herein, we show for the first time that a single atom change, hydrogen to halogen, at one of the tyrosine residues can increase the cellular entry of ∼28 kDa green fluorescent protein (GFP) in mammalian cells. The protein uptake is facilitated by a receptor-mediated endocytosis and the cargo can be released effectively into cytosol by co-treatment with the endosomolytic peptide ppTG21.
Keywords: endocytosis; green fluorescent protein; halogens; membrane transport; tRNA synthetase.
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