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Enzymatic Cleavage of Branched Peptides for Targeting Mitochondria

Most of the reported mitochondria-targeting molecules are lipophilic and cationic, and thus they may become cytotoxic with accumulation. Here we show enzymatic cleavage of branched peptides that carry negative charges for targeting mitochondria. Conjugating a well-established protein tag (i.e., FLAG-tag) to self-assembling motifs affords the precursors that form micelles. Enzymatic cleavage of the hydrophilic FLAG motif (DDDDK) by enterokinase (ENTK) turns the micelles to nanofibers. After being taken up by cells, the micelles, upon the action of intracellular ENTK, turn into nanofibers to locate mainly at mitochondria. The micelles of the precursors are able to deliver cargos (either small molecules or proteins) into cells, largely to mitochondria and within 2 h. Preventing ENTK proteolysis diminishes mitochondria targeting. As the first report of using enzymatic self-assembly for targeting mitochondria and delivery cargos to mitochondria, this work illustrates a fundamentally new way to target subcellul...

Authors:   Hongjian He; Jiaqing Wang; Huaimin Wang; Ning Zhou; Dongsik Yang; Douglas R. Green; Bing Xu
Journal:   Journal of the American Chemical Society
Year:   2018
DOI:   10.1021/jacs.7b11582
Publication date:   19-Jan-2018
Facts, background information, dossiers
  • protein tag
  • peptides
  • nanofibers
  • cells
More about American Chemical Society Publications
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