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Internalization and Accumulation in Dendritic Cells of a Small pH‐Activatable Glycomimetic Fluorescent Probe as Revealed by Spectral Detection
Authors:Prof. Zoran Arsov  Prof. Urban Švajger  Prof. Janez Mravljak  Prof. Stane Pajk  Anita Kotar  Dr. Iztok Urbančič  Prof. Janez Štrancar  Prof. Marko Anderluh
Affiliation:1. Laboratory of Biophysics, Department of Condensed Matter Physics, Jozef Stefan Institute, Ljubljana, Slovenia;2. Center of Excellence NAMASTE, Ljubljana, Slovenia;3. Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia;4. Department of Medicinal Chemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia;5. Slovenian NMR Centre, National Institute of Chemistry, Ljubljana, Slovenia
Abstract: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.
Keywords:dendritic cells  fluorescent probes  glycoconjugates  internalization  lectins
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