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Fluorinated Man9 as a high mannose mimetic to unravel its recognition by DC-SIGN using NMR

IIQ

Adrián Silva-Díaz, Jonathan Ramírez-Cárdenas, Juan C. Muñoz-García, M. Carmen de la Fuente, Michel Thépaut, Franck Fieschi, Javier Ramos-Soriano, Jesús Angulo and Javier Rojo J. Am. Chem. Soc. 2023, Vol. 145, 26009-26015

Lectins are capable of reading out the structural information contained in carbohydrates through specific recognition processes. Determining the binding epitope of the sugar is fundamental to understanding this recognition event. Nuclear magnetic resonance (NMR) is a powerful tool to obtain this structural information in solution; however, when the sugar involved is a complex oligosaccharide, such as high mannose, the signal overlap found in the NMR spectra precludes an accurate analysis of the interaction. The introduction of tags into these complex oligosaccharides could overcome these problems and facilitate NMR studies. Here, we show the preparation of the Man9 of high mannose with some fluorine tags and the study of the interaction with its receptor, dendritic cell specific intercellular adhesion molecule-3-grabbing nonintegrin (DCSIGN). This fluorinated ligand has allowed us to apply heteronuclear two-dimensional (2D) ¹H,¹⁹F STD-TOCSYreF NMR experiments, using the initial slope approach, which has facilitated the analysis of the Man₉/DC-SIGN interaction, unequivocally providing the binding epitope.

https://pubs.acs.org/doi/10.1021/jacs.3c06204

 

 

Adrián Silva y Jonathan Ramírez