Artículos (Química Orgánica)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/10924

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Examinando Artículos (Química Orgánica) por Agencia financiadora "Centre national de la recherche scientifique (CNRS). France"

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    Acceso AbiertoArtículo
    sp2-Iminosugar Glycolipids as Inhibitors of Lipopolysaccharide-mediated Human Dendritic Cell Activation in Vitro and of Acute Inflammation in Mice in Vivo
    (Elsevier, 2019) Schaeffer, Evelyne; Sánchez Fernández, Elena Matilde; Gonçalves-Pereira, Rita; Flacher, Vincent; Lamon, Delphine; Duval, Monique; Fauny, Jean Daniel; García Fernández, José Manuel; Mueller, Christopher G.; Ortiz Mellet, Carmen; Universidad de Sevilla. Departamento de Química orgánica; Centre national de la recherche scientifique (CNRS). France; Ministerio de Economía y Competitividad (MINECO). España
    Glycolipid mimetics consisting of a bicyclic polyhydroxypiperidine-cyclic carbamate core and a pseudoanomeric hydrophobic tail, termed sp2-iminosugar glycolipids (sp2-IGLs), target microglia during neuroinflammatory processes. Here we have synthesized and investigated new variants of sp2-IGLs for their ability to suppress the activation of human monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS) signaling through Toll-like receptor 4. We report that the best lead was (1R)-1-dodecylsulfonyl-5N,6O-oxomethylidenenojirimycin (DSO2-ONJ), able to inhibit LPS-induced TNFα production and maturation of DCs. Immunovisualization experiments, using a mannoside glycolipid conjugate (MGC) that also suppress LPS-mediated DC activation as control, evidenced a distinct mode of action for the sp2-IGLs: unlike MGCs, DSO2-ONJ did not elicit internalization of the LPS co-receptor CD14 or induce its co-localization with the Toll-like receptor 4. In a mouse model of LPS-induced acute inflammation, DSO2-ONJ demonstrated anti-inflammatory activity by inhibiting the production of the pro-inflammatory interleukin-6. The ensemble of the data highlights sp2-IGLs as a promising new class of molecules against inflammation by interfering in Toll-like receptor intracellular signaling.
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    Acceso AbiertoArtículo
    Synthesis of β-galactosylamides as Ligands of the Peanut Lectin. Insights into the Recognition Process
    (Elsevier, 2017) Cano, María Emilia; Varela, Oscar; García Moreno, M. Isabel; García Fernández, José Manuel; Kovensky, José; Uhrig, María Laura; Universidad de Sevilla. Departamento de Química orgánica; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Argentina; Centre national de la recherche scientifique (CNRS). France; Ministerio de Economía y Competitividad (MINECO). España; Junta de Andalucía; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
    The synthesis of mono and divalent β-galactosylamides linked to a hydroxylated chain having a C2 symmetry axis derived from L-tartaric anhydride is reported. Reference compounds devoid of hydroxyl groups in the linker were also prepared from β-galactosylamine and succinic anhydride. After functionalization with an alkynyl residue, the resulting building blocks were grafted onto different azide-equipped scaffolds through the copper catalyzed azide-alkyne cycloaddition. Thus, a family of structurally related mono and divalent β-N-galactopyranosylamides was obtained and fully characterized. The binding affinities of the ligands towards the model lectin PNA were measured by the enzyme-linked lectin assay (ELLA). The IC50 values were significantly higher than that of galactose but the presence of hydroxyl groups in the aglycone chain improved lectin recognition. Docking and molecular dynamics experiments were in accordance with the hypothesis that a hydroxyl group properly disposed in the linker could mimic the Glc O3 in the recognition process. On the other hand, divalent presentation of the ligands led to lectin affinity enhancements.