104430-65-1Relevant academic research and scientific papers
ANTIBACTERIAL ANTISENSE AGENTS
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Page/Page column 50, (2020/06/19)
The invention relates to improved ANTISENSE agents for the treatment of gram-negative bacterial infections. Compounds of the invention utilise an Antibiotic-Assisted Translocation; AAT' platform to improve influx into bacterial cells through enhanced permeability, providing improved intracellular exposure of the ANTISENSE AGENT and superior treatment of the infection.
Total synthesis of n-acetylglucosamine-1,6-anhydro-n- acetylmuramylpentapeptide and evaluation of its turnover by ampd from escherichia coli
Hesek, Dusan,Lee, Mijoon,Zhang, Weilie,Noll, Bruce C.,Mobashery, Shahriar
supporting information; experimental part, p. 5187 - 5193 (2009/09/30)
The bacterial cell wall is recycled extensively during the course of cell growth. The first recycling event involves the catalytic action of thelytic transglycosylase enzymes, which produce an uncommon 1,6-anhydropy ranose moiety during separation of the muramyl residues from the peptidoglycan, the major constituent of the cell wall. This product, an N-acetyl-β-D-glucosamine- (1→4)-1,6-anhydro-N-acetyl-β-Dmuramylpeptide, is either internalized to initiate the recycling process or diffuses into the milieu to cause stimulation of the pro-inflammatory responses by the host. We report the total syntheses of N-acetyl-β-Dglucosamine-( 1→4)-1,6-anhydro-N-acetyl- β-D-muramyl-L-Ala-γ-D-Glu-meso-DAP-D-Ala-D-Ala (compound 1, the product of lytic transglycosylase action on the cell wall of Gram-negative bacteria) and N-acetyl-β-Dglucosamine-( 1→4)-1,6-anhydro-N-acetyl- β-D-muramyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala (compound 2, from lytic transglycosylase action on the cell wall of Gram-positive bacteria). The syntheses were accomplished in 15 linear steps. Compound 1 is shown to be a substrate of the AmpD enzyme of the Gram-negative bacterium Escherichia coli, anenzyme that removes the peptide from the disaccharide scaffold in the e arly cytoplasmic phase of cell wall turnover.
Synthesis of diaminopimelic acid containing peptidoglycan fragments and tracheal cytotoxin (TCT) and investigation of their biological functions
Kawasaki, Akiko,Karasudani, Yukie,Otsuka, Yuji,Hasegawa, Mizuho,Inohara, Naohiro,Fujimoto, Yukari,Fukase, Koichi
experimental part, p. 10318 - 10330 (2009/11/30)
Bacterial cell wall peptidoglycan (PGN) is a potent immunostimulator and immune adjuvant. The PGN of Gram-negative bacteria and some Gram-positive bacteria contain meso-diaminopimelic acid (meso-DAP), and we have recently shown that the intracellular protein Nodi is a PGN receptor and recognizes DAPcontaining peptides. In this study, we achieved the synthesis of DAP-containing PGN fragments, including the first chemical synthesis of tracheal cytotoxin (TCT), GlcNAc-(β1-4)-(anhydro) Mur-NAc-L-Ala-γ-D-Glu-meso- DAP-D-Ala, and a repeating-unit of DAP-type PGN, GlcNAc-(β1-4)-MurNAc-L- Ala-γ-D-Glu-meso-DAP-D-Ala. For the synthesis of PGN fragments, we first established a new synthetic method for an orthogonally protected meso-DAP derivative, and then we constructed the glycopeptide structures. The ability of these fragments to stimulate human Nodi, as well as differences in Nodi recognition of the variety of synthesized ligand structures were examined. The results showed that the substitution of the N terminus of iE-DAP is necessary for stronger Nodi recognition, but the structure of the substituent seems not to be strictly recognized. The importance of the carboxyl group at the 2-position of DAP for human Nod1 stimulation was also shown.
