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Browsing INETI by Author "Alves, Susana"

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  • Síntese e avaliação biológica de novas saponinas imunoactivas=|Syntheses and biological evaluation of novel Immunoactive saponins
    Publication . Costa, Maria do Céu; Eleutério, I.; Ramos, Susana Sofia; Alves, Susana; Cardoso, F. H.; Ley, S.; Schmidt, R. R.
    QS21 is a natural saponin extracted with water from the bark of endemic trees of South America which has been shown to play a key role as vaccine adjuvant. The aim of this study was to determine if simpler synthetic analogues of QS-21 could induce similar advantageous immune responses. For this purpose we designed and synthesized both the cholestanyl- and amirinyl-3-β-O-(β-D-xylopyranosyl)-(1 →3)-[(β-D-galactopyranosyl)-(1→2)]-6-β-D-glucuronic acid 1 and 2, respectively, by first attaching the glucoside residues to the terpene and then extending the sugar chain. The secretion of the pro-inflammatory cell mediators IL-6 and IL-1, TNF-{460} and NO and the IgG serum levels after in vivo stimulation of APCs with 1 and 2, were used to assess their adjuvant activity in vitro. Compounds 1 and 2 were stronger cytotoxic for murine J744A. 1 tumor cells than QS21 and showed less undesired hemolytic activity on red blood cells than QS-21, but did not induce strong cytotoxic CD8 responses after a single injection, while immunization with ovalbumin and QS-21 did. Although synthetic analogues 1 and 2 show good adjuvant activity in vitro it is probably the lack of the aldehyde group and the acyl chain that negatively affects the simplified saponins properties to induce active cytotoxic T cells in mice.
    2005Journal article Open access Show more