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    BODIPY-Labeled DC-SIGN-Targeting Glycodendrons Efficiently Internalize and Route to Lysosomes in Human Dendritic Cells

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    Glycodendrons bearing nine copies of mannoses or fucoses have been prepared by an efficient convergent strategy based on Cu(I) catalyzed azide−alkyne cycloaddition (CuAAC). These glycodendrons present a well-defined structure and have an adequate size and shape to interact efficiently with the C-type lectin DCSIGN. We have selected a BODIPY derivative to label these glycodendrons due to its interesting physical and chemical properties as chromophore. These BODIPY-labeled glycodendrons were internalized into dendritic cells by mean of DC-SIGN. The internalized mannosylated and fucosylated dendrons are colocalized with LAMP1, which suggests routing to lysosomes. The interaction of these glycodendrons with DC-SIGN at the surface of dendritic cells did not induce maturation of the cells. Signaling analysis by checking different cytokines indicated also the lack of induction the expression of inflammatory and noninflamatory cytokines by these second generation glycodendrons.We would like to acknowledge the financial support by the MICINN of Spain CTQ2008-01694, CTQ2010-20303 and CTQ2011-23410/BQU, the EU RTN CARMUSYS (PITNGA- 2008-213592), and the European FEDER funds. J.J.G.-V. was supported by VENI NWO-ALW (Grant 863.08.020) and Astma Fonds (3.2.10.040).Peer Reviewe
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