Peptidoglycan (PGN) is a major component of bacterial cell wall and is recognized as a potent immunostimulant. The PGN in the cell envelope of Mycobacterium Tuberculosishas been shown to possess ...several unique characteristics including the presence of N-glycolyl groups (in addition to N-acetyl groups) in the muramic acid residues, and amidation of the free carboxylic acid of d-Glu or of meso-DAP in the peptide chains. Using a newly developed, highly stereoselective, chemoenzymatic approach for the synthesis of meso-DAP in peptide stems, we successfully synthesized for the first time, a series of MycobacteriumPGN fragments that include both mono- and disaccharides of MurNGlyc or 1,6-anhydro-MurNGlyc, as well as peptide-amidated variants. The ability of these PGN fragments to stimulate the immune system through activation of human Nod1 and Nod2 was examined. The PGN fragments were found to modulate immune stimulation, specifically, amidation at the d-Glu and meso-DAP in the peptide stem strongly reduced hNod1 activation. This effect was dependent on modification position. Additionally, N-glycolyl (instead of acetyl) of muramic acid was associated with slightly reduced human Nod1 and Nod2 stimulatory capabilities.
In vivo gold complex catalysis in living mice is described by K. Tanaka and co‐workers in their Communication on page 3579 ff. When attached to a glycocluster, gold catalysts can be delivered to a ...target organ in a higher organism where they perform a chemical transformation. This approach could enable the use of organometallic catalysts in therapy or diagnostics as they could catalyze the uncaging of therapeutic enzymes or the generation of active drugs at a target organ.
Invivo gold complex catalysis in living mice is described by K. Tanaka and co-workers in their Communication on page3579ff. When attached to a glycocluster, gold catalysts can be delivered to a ...target organ in a higher organism where they perform a chemical transformation. This approach could enable the use of organometallic catalysts in therapy or diagnostics as they could catalyze the uncaging of therapeutic enzymes or the generation of active drugs at a target organ.
A general probe designed to induce a cascading sequence of reactions on a target protein was efficiently synthesized. The cascading reaction sequence involved (i) ligand-directed ...azaelectrocyclization with lysine and (ii) the autooxidation-induced release of a fluorescence quencher from the labeled protein. The probe was linked to a cyclic RGDyK peptide to enable the selective visualization of integrin α
V
β
3
on the surfaces of live cells.
A general probe designed to induce a cascading sequence of reactions on a target protein was efficiently synthesized.
In article number 1801479, Shinzaburo Noguchi, Katsunori Tanaka, and co‐workers use a click‐to‐sense probe to detect acrolein, which is universally produced by cancer cells under oxidative stress, ...within five minutes at room temperature. All cancer types tested are imaged and discriminated through multiple cascade reactions in the living tissue of human patients. This probe can be used to quickly and accurately diagnose cancer morphology during breast‐conserving surgery, by reforming the conventional pathological methods.
The unsaturated ester aldehyde, (
E
)-3-alkoxycarbonyl-5-phenyl-2,4-dienal, was efficiently dimerized by applying the strain-promoted double-click reaction with
sym
...-dibenzo-1,5-cyclooctadiene-3,7-diyne. The resulting dimerized probe was sequentially reacted first with one peptide molecule and then with a protein or the amino groups on the surface of a live cell through double azaelectrocyclization to achieve highly efficient bioconjugation.
The unsaturated ester aldehyde, (
E
)-3-alkoxycarbonyl-5-phenyl-2,4-dienal, was developed to achieve highly efficient bioconjugation between the biological amines.
Acrolein, a highly toxic a,b-unsaturated aldehyde, has been a longstanding key biomarker associated with a range of disorders under oxidative stress conditions. The conventional analytical method for ...detection of acrolein, e.g. HPLC analysis after derivatization with 3-aminophenol under harsh reaction conditions, is not suitable for high-throughput assay and inconvenient for measurement in clinical practice. A monoclonal antibody can be used for detection of acrolein-lysine adducts; however this method is time-consuming and expensive. Consequently, developing new analytical tools that are straightforward, cost-effective, and selective for acrolein detection in live cells remains highly important for the diagnosis and therapeutic treatment of oxidative stress-related diseases. Herein we demonstrated for the first time that phenyl azide can rapidly and selectively react with acrolein in a “click” manner to provide 4-formyl-1,2,3-triazoline and 4-formyl-1,2,3-triazole derivatives, which represents an unexplored reactivity of aryl azides. Acrolein could be ubiquitously generated in oxidatively stressed cells. When oxidatively stressed cells treated with TAMRA-labeled phenyl azide, the generated acrolein reacted to yield “clicked” products, which could be selectively taken up by the cells. This could potentially lead to a new tool for both effectively detecting acrolein level and directly imaging live cells that are under oxidative stress conditions. The detection method developed here is not only convenient but also the simple structures of the azide probe allows for functional groups other than fluorescent to be readily linked to aryl azide to image, examine, or target the cells associated with oxidative stress.
Metal complex catalysis within biological systems is largely limited to cell and bacterial systems. In this work, a glycoalbumin-AuIII complex was designed and developed that enables organ-specific, ...localized propargyl ester amidation with nearby proteins within live mice. The targeted reactivity can be imaged through the use of Cy7.5- and TAMRA-linked propargyl ester based fluorescent probes. This targeting system could enable the exploitation of other metal catalysis strategies for biomedical and clinical applications.
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