Pseudosaccharide Functionalized Dendrimers as Potent Inhibitors of DC-SIGN Dependent Ebola Pseudotyped Viral Infection

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• 作者：Joanna Luczkowiak ; Sara Sattin ; Ieva Sutkevic虒iu虆te虈 ; Jose虂 Juan Reina ; Macarena Sa虂nchez-Navarro ; Michel The虂paut ; Lorena Marti虂nez-Prats ; Anna Daghetti ; Franck Fieschi ; Rafael Delgado ; Anna Bernardi ; Javier Rojo
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：July 20, 2011
• 年：2011
• 卷：22
• 期：7
• 页码：1354-1365
• 全文大小：1077K
• 年卷期：v.22,no.7(July 20, 2011)
• ISSN：1520-4812

文摘

The development of compounds with strong affinity for the receptor DC-SIGN is a topic of remarkable interest due to the role that this lectin plays in several pathogen infection processes and in the modulation of the immune response. DC-SIGN recognizes mannosylated and fucosylated oligosaccharides in a multivalent manner. Therefore, multivalent carbohydrate systems are required to interact in an efficient manner with this receptor and compete with the natural ligands. We have previously demonstrated that linear pseudodi- and pseudotrisaccharides are adequate ligands for DC-SIGN. In this work, we show that multivalent presentations of these glycomimetics based on polyester dendrons and dendrimers lead to very potent inhibitors (in the nanomolar range) of cell infection by Ebola pseudotyped viral particles by blocking DC-SIGN receptor. Furthermore, SPR model experiments confirm that the described multivalent glycomimetic compounds compete in a very efficient manner with polymannosylated ligands for binding to DC-SIGN.