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Internalization and Accumulation in Dendritic Cells of a Small pH-Activatable Glycomimetic Fluorescent Probe as Revealed by Spectral Detection

DC‐SIGN, an antigen‐uptake receptor in dendritic cells (DCs), has a clear role in the immune response but, conversely, can also facilitate infection by providing entry of pathogens into DCs. The key action in both processes is internalization into acidic endosomes and lysosomes. Molecular probes tha...

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Published in:Chembiochem : a European journal of chemical biology 2015-12, Vol.16 (18), p.2660-2667
Main Authors: Arsov, Zoran, Švajger, Urban, Mravljak, Janez, Pajk, Stane, Kotar, Anita, Urbančič, Iztok, Štrancar, Janez, Anderluh, Marko
Format: Article
Language:English
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Summary:DC‐SIGN, an antigen‐uptake receptor in dendritic cells (DCs), has a clear role in the immune response but, conversely, can also facilitate infection by providing entry of pathogens into DCs. The key action in both processes is internalization into acidic endosomes and lysosomes. Molecular probes that bind to DC‐SIGN could thus provide a useful tool to study internalization and constitute potential antagonists against pathogens. So far, only large molecules have been used to directly observe DC‐SIGN‐mediated internalization into DCs by fluorescence visualization. We designed and synthesized an appropriate small glycomimetic probe. Two particular properties of the probe were exploited: activation in a low‐pH environment and an aggregation‐induced spectral shift. Our results indicate that small glycomimetic molecules could compete with antigen/pathogen for binding not only outside but also inside the DC, thus preventing the harmful action of pathogens that are able to intrude into DCs, for example, HIV‐1. A small “smart” glycomimetic fluorescent probe has been synthesized to monitor internalization by the DC‐SIGN receptor in dendritic cells (DCs). Its activation and accumulation in low‐pH cell structures were spectrally detected. Such molecules could compete with pathogens for binding both outside and inside DCs.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.201500376