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An assay for functional dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) inhibitors of human dendritic cell adhesion
Authors:Nataša Obermajer  Urban Švajger  Sara Sattin  Marko Anderluh
Institution:a Department of Biotechnology, Jo?ef Stefan Institute, SI-1000 Ljubljana, Slovenia
b Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, SI-1000 Ljubljana, Slovenia
c Blood Transfusion Center of Slovenia, 1000 Ljubljana, Slovenia
d Dipartimento di Chimica Organica e Industriale, Università di Milano, I-20133 Milano, Italy
e Department of Medicinal Chemistry, Faculty of Pharmacy, University of Ljubljana, SI-1000 Ljubljana, Slovenia
Abstract:We report a new dendritic cell adhesion assay, using either immature or mature dendritic cells, for identifying functional dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) inhibitors. Because immature dendritic cells are responsible for pathogen binding and invasion, this in vitro assay provides an important link between in vitro results and pathogen-based in vivo assays. Furthermore, this assay does not require laborious expression, refolding, and purification of DC-SIGN carbohydrate recognition domain or extracellular domain as receptor-based assays. The assay power evaluated with Z and Z′ parameters enables screening of compound libraries and determination of IC50 values in the first stage of DC-SIGN inhibitor development.
Keywords:DC-SIGN  Dendritic cell  Anti-infectives  Dendritic cell-based assay
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