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...
Hongjian He; Jiaqing Wang; Huaimin Wang; Ning Zhou; Dongsik Yang; Douglas R. Green; Bing Xu
We recently generalized the formerly alignment-dependent multivariate image analysis applied to quantitative structure–activity relationships (MIA-QSAR) method through the application of the discrete Fourier transform (DFT), allowing for its application to noncongruent and structurally dive ... more
Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses. It is catalyzed by a class of enzymes known as poly-ADP-ribose polymerases (PARPs). In particular, PARP1 is ... more
This review focuses on the type A cytochrome c oxidases (CcO), which are found in all mitochondria and also in several aerobic bacteria. CcO catalyzes the respiratory reduction of dioxygen (O2) to water by an intriguing mechanism, the details of which are fairly well understood today as a r ... more
Rohm and Haas Powder Coatings is delighted to announce that its Reading, Pennsylvania, facility is the first site in the world to receive the RCMS® Site Certification awarded by the American Chemical Council (ACC).
When Raj Gupta, Chairman and CEO of Rohm and Haas Company, became Chairman ... more