1373347-10-4Relevant academic research and scientific papers
A Remote Secondary Binding Pocket Promotes Heteromultivalent Targeting of DC-SIGN
Bachem, Gunnar,Domeniconi, Gary,Ernst, Beat,Fuchsberger, Felix F.,Hauck, Dirk,Lefebre, Jonathan,Marti, Marcelo A.,Modenutti, Carlos,Rademacher, Christoph,Rentzsch, Mareike,Schnirch, Lennart,Schulze, Jessica,Schwardt, Oliver,Seeberger, Peter H.,Seitz, Oliver,Titz, Alexander,Wamhoff, Eike-Christian,Wawrzinek, Robert,Zhang, Hengxi,Br?utigam, Maria,Guberman, Mónica
supporting information, p. 18977 - 18988 (2021/11/26)
Dendritic cells (DC) are antigen-presenting cells coordinating the interplay of the innate and the adaptive immune response. The endocytic C-type lectin receptors DC-SIGN and Langerin display expression profiles restricted to distinct DC subtypes and have emerged as prime targets for next-generation immunotherapies and anti-infectives. Using heteromultivalent liposomes copresenting mannosides bearing aromatic aglycones with natural glycan ligands, we serendipitously discovered striking cooperativity effects for DC-SIGN+ but not for Langerin+ cell lines. Mechanistic investigations combining NMR spectroscopy with molecular docking and molecular dynamics simulations led to the identification of a secondary binding pocket for the glycomimetics. This pocket, located remotely of DC-SIGN's carbohydrate bindings site, can be leveraged by heteromultivalent avidity enhancement. We further present preliminary evidence that the aglycone allosterically activates glycan recognition and thereby contributes to DC-SIGN-specific cell targeting. Our findings have important implications for both translational and basic glycoscience, showcasing heteromultivalent targeting of DCs to improve specificity and supporting potential allosteric regulation of DC-SIGN and CLRs in general.
MANNOSIDE COMPOUNDS AND METHODS OF USE THEREOF
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Page/Page column 71, (2012/08/28)
The present invention encompasses compounds and methods for treating urinary tract infections.
