ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTDesign of Bifunctional Antibiotics that Target Bacterial rRNA and Inhibit Resistance-Causing EnzymesSteven J. Sucheck, Andrew L. Wong, Kathryn M. Koeller, David D. Boehr, Kari-ann Draker, Pamela Sears, Gerard Wright, Chi-Huey WongView Author Information Department Chemistry The Skaggs Institute for Chemical Biology, Scripps Research 10550 North Torrey Pines Road, La Jolla, California 92037 Antimicrobial Centre, Biochemistry McMaster...

2-Alkyl-1,2-benzisoselenazol-3(2H)-ones, represented by ebselen (1a), are being studied intensively for a range of medicinal applications. We describe both new thermal and photoinduced copper-mediated cross-coupling between potassium selenocyanate (KSeCN) N-substituted ortho-halobenzamides to form 2-alkyl-1,2-benzisoselenazol-3(2H)-ones containing C–Se–N bond. The copper ligand (1,10-phenanthroline) facilitates C–Se bond formation during heating via mechanism that likely involves atom...

Ebselen (EBS) is an organo-selenium-containing compound that has anti-inflammatory, antitumor, and antibacterial properties. EBS being explored as a possible treatment for reperfusion injury stroke under clinical trials mimetic of lithium the bipolar disorder [Mota et al. Synapse 2020, 74 (7), 1−6] noise-induced hearing loss result these actives [Martini J. Psychiatr. Res. 2019, 109, 107−117. Slusarczyk Neural Regener. 17 1255–1261. Thangamani PLoS One 2015, 10 e0133877. Kil Lancet 2017, 390...

The complex signaling mechanisms in red blood cells (RBCs) enable them to adapt physiological stresses such as exposure low O2 levels, metabolic demands, oxidative stress, and shear stress. Since Ca2+ is a crucial determinant of RBC fate, various ion channels, pumps, exchangers regulate the delicate balance influx efflux RBCs. Elevated intracellular can activate processes membrane phospholipid scrambling alter deformability, which essential for effective capillary transit. However, dynamic...

Carbohydrates are generally considered to be poorly immunogenic. Therefore, new approaches for enhancing their immunogenicity important the development of carbohydrates as vaccine components. We hypothesized that conjugation an l-rhamnose (Rha) moiety a carbohydrate antigen would enhance antigenicity in mice possessing anti-Rha antibodies via antibody-dependent uptake mechanism. To explore this hypothesis, we synthesized single-molecule three-component containing GalNAc-O-Thr (Tn)...

Generation of a CD8(+) response to extracellular antigen requires processing the by presenting cells (APC) and cross-presentation T cell receptors via MHC class I molecules. Cross-presentation is facilitated efficient uptake followed immune-complex-mediated maturation APCs. We hypothesize that improved glycopeptide sequence containing epitope could be achieved delivering it on liposome surface decorated with an immune complex-targeting ligand, l-Rhamnose (Rha) epitope. synthesized...

Tuberculosis (TB) is an epidemic disease and the growing burden of multidrug-resistant (MDR) TB world wide underlines need to discover new drugs treat disease.

MUC1 variable number tandem repeats (VNTRs) conjugated to tumor-associated carbohydrate antigens (TACAs) have been shown break self-tolerance in humanized transgenic mice. Therefore, we hypothesize that a VNTR TACA-conjugate can be successfully formulated into liposome-based anticancer vaccine. The immunogenicity of the vaccine should further augmented by incorporating surface-displayed l-rhamnose (Rha) epitopes onto liposomes take advantage natural antibody-dependent antigen uptake...

New 2-aminothiophenes (2AT) were identified with MICs = 0.23–0.44 μM against drug sensitive and resistant strains of<italic>Mycobacterium tuberculosis</italic>.

Utilizing natural antibodies to augment vaccine immunogenicity is a promising approach toward cancer immunotherapy. Anti-rhamnose (anti-Rha) are some of the most common anti-carbohydrate present in human serum. Therefore, rhamnose can be utilized as targeting moiety for rhamnose-containing prepare an effective formulation. It was shown previously that anti-Rha antibody generated mice binds effectively with Rha-conjugated and picked up by antigen presenting cells (APCs) through stimulatory Fc...

Functional single-stranded oncogenic mRNAs such as the breakpoints of PAX3 – FKHR and Bcr Abl oncogenes bind selectively with high affinity to naturally occurring, well synthetic, aminoglycosides. The latter, neamine-derived compounds were designed mimic their natural counterparts in recognizing RNA (the proposed mode binding a phosphodiester is shown) obtained by parallel synthesis.

With the surge of antibiotic resistance in bacteria, need for a larger arsenal effective antibiotics and vaccines has drastically increased past decades. Antibiotics like can benefit from significant potentiation when used combination with adjuvants. Antibiotic adjuvants allow gram-positive bacteria (GPB) specific treatments to be against gram-negative (GNB) infections, minimal antimicrobial (AMR). In case vaccines, they modulation increase immune response. Lipopeptides are molecules choice...

Double duty: Dimeric aminoglycoside antibiotics were designed by linking neamine or nebramine cores with various tethers differing in length and composition. The resulting dimeric aminoglycosides displayed high affinity for the 16S A site of ribosomal RNA (a representation complex is shown here) effective against aminoglycoside-resistant bacterial strains. Supporting information this article available on WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z53225_s.pdf from author. Please...

Previous studies identified ebselen as a potent in vitro and vivo inhibitor of the Mycobacterium tuberculosis (Mtb) antigen 85 (Ag85) complex, comprising three homologous enzymes required for biosynthesis mycobacterial cell wall. In this study, Mtb Ag85C enzyme was cocrystallized with azido adamantyl derivatives, resulting two crystallographic structures 2.01 1.30 Å resolution, respectively. Both displayed anticipated covalent modification solvent accessible, noncatalytic Cys209 residue...

Long treatment times, poor drug compliance, and natural selection during of Mycobacterium tuberculosis (Mtb) have given rise to extensively drug-resistant (XDR-TB). As a result, there is need identify new antituberculosis targets. Mtb GlgE maltosyl transferase involved in α-glucan biosynthesis. Mutation increases the concentration maltose-1-phosphate (M1P), one substrate for GlgE, causing rapid cell death. We designed 2,5-dideoxy-3-O-α-d-glucopyranosyl-2,5-imino-d-mannitol (9) act as an...

The total syntheses of bleomycin A2 (1) by two routes are described. final step in the synthesis involves methylation demethyl (2). This derivative is interest mechanistically, and can also provide access to other bleomycins via its known chemical conversion bleomycinic acid. Accordingly, synthetic strategy presented represents a particularly versatile approach for elaboration wide variety BLM congeners. Bleomycin was constructed from five key intermediates, which...

The anthrax lethal factor (LF), a Zn-dependent endopeptidase, is considered the dominant virulence of anthrax. Because pharmacological inhibition catalytic activity LF plausible mechanism for preventing lethality anthrax, high-throughput screening experiment based on LF-catalyzed cleavage fluorescent substrate was performed to identify novel inhibitors LF. RNA-targeting antibiotics, neomycin B and some synthetic dimeric aminoglycosides, were found be nanomolar active-site