956479-18-8

Upstream product

• 632-46-2 2,6-dimethylbenzoic acid 
• 114480-07-8 (S)-2-((S)-2-(((benzyloxy)carbonyl)amino)-3-phenylpropanamido)-6-((tert-butoxycarbonyl)amino)hexanoic acid 
• 1161-13-3 N-Cbz-L-Phe 
• 1342259-39-5 Fmoc-Lys(Boc)-BMK 
• 71989-26-9 Fmoc-Lys(tert-butoxycarbonyl) 

Downstream Products

• 56-87-1 L-lysine 
• 63-91-2 L-phenylalanine 

Relevant academic research and scientific papers

CT Imaging of Enzymatic Activity in Cancer Using Covalent Probes Reveal a Size-Dependent Pattern

X-ray CT instruments are among the most available, efficient, and cost-effective imaging modalities in hospitals. The field of CT molecular imaging is emerging which relies mainly on the detection of gold nanoparticles and iodine-containing compounds directed to tagging a variety of abundant biomolecules. Here for the first time we attempted to detect enzymatic activity, while the low sensitivity of CT scanners to contrast reagents made this a challenging task. Therefore, we developed a new class of nanosized cathepsin-targeted activity-based probes (ABPs) for functional CT imaging of cancer. ABPs are small molecules designed to covalently modify enzyme targets in an activity-dependent manner. Using a CT instrument, these novel probes enable detection of the elevated cathepsin activity within cancerous tissue, thus creating a direct link between biological processes and imaging signals. We present the generation and biochemical evaluation of a library of ABPs tagged with different sized gold nanoparticles (GNPs), with various ratios of cathepsin-targeting moiety and a combination of different polyethylene glycol (PEG) protective layers. The most potent and stable GNP-ABPs were applied for noninvasive cancer imaging in mice. Surprisingly, detection of CT contrast from the tumor had reverse correlation to GNP size and the amount of targeting moiety. Interestingly, TEM images of tumor sections show intercellular lysosomal subcellular localization of the GNP-ABPs. In conclusion, we demonstrate that the covalent linkage is key for detection using low sensitive imaging modalities and the utility of GNP-ABPs as a promising tool for enzymatic-based CT imaging.

PHOTODYNAMIC QUENCHED ACTIVITY BASED PROBES AND USES THEREOF IN IMAGING AND TARGETED THERAPY

The present invention relates to compounds comprising photosensitizer, compositions comprising the same as well as uses and methods thereof for detection and for treatment using photodynamic therapy.

Disruption of glycolytic flux is a signal for inflammasome signaling and pyroptotic cell death

When innate immune cells such as macrophages are challenged with environmental stresses or infection by pathogens, they trigger the rapid assembly of multi-protein complexes called inflammasomes that are responsible for initiating pro-inflammatory responses and a form of cell death termed pyroptosis. We describe here the identification of an intracellular trigger of NLRP3-mediated inflammatory signaling, IL-1b production and pyroptosis in primed murine bone marrow-derived macrophages that is mediated by the disruption of glycolytic flux. This signal results from a drop of NADH levels and induction of mitochondrial ROS production and can be rescued by addition of products that restore NADH production. This signal is also important for host-cell response to the intracellular pathogen Salmonella typhimurium, which can disrupt metabolism by uptake of host-cell glucose. These results reveal an important inflammatory signaling network used by immune cells to sense metabolic dysfunction or infection by intracellular pathogens.