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Unraveling sugar binding modes to DC-SIGN by employing fluorinated carbohydrates

Unraveling sugar binding modes to DC-SIGN by employing fluorinated carbohydrates
Unraveling sugar binding modes to DC-SIGN by employing fluorinated carbohydrates
A 19F-NMR-based method is employed to assess the binding preferences and interaction details of a library of synthetic fluorinated monosaccharides towards DC-SIGN, a lectin of biomedical interest, which is involved in different viral infections, including HIV and Ebola, and is able to recognize a variety of self- and non-self-glycans. The employed strategy allows not only to screen a mixture of compounds, but also to obtain valuable information on the specific sugar-protein interactions. The analysis of the data demonstrates that monosaccharides Fuc, Man, Glc and Gal are able to bind DC-SIGN, although with decreasing affinity. Moreover, a new binding mode between Man moieties and DC-SIGN, which might have biological implications, has also been detected for the first time. The combination of the 19F with standard 1H-STD-NMR data, assisted by MD simulations, permitted to successfully define this new binding epitope, in which Man coordinates a Ca2+ ion of the lectin CRD through the axial OH-2 and equatorial OH-3 groups, thus mimicking the Fuc/DC-SIGN binding architecture.
NMR, molecular recognition, lectin, glycomimetics, DC-SIGN, C-type lectins, fluorinated sugars, 19F-NMR, screening, molecular dynamics
1420-3049
Martínez, J. Daniel
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Valverde, Pablo
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Delgado, Sandra
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Romanò, Cecilia
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Linclau, Bruno
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Reichardt, Niels C.
00b4a72e-ca65-4ea8-a28c-deb3d8ec65fd
Oscarson, Stefan
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Ardá, Ana
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Jiménez-Barbero, Jesús
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Cañada, F. Javier
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Martínez, J. Daniel
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Valverde, Pablo
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Delgado, Sandra
50db02aa-4878-4d73-be72-634179f07fc6
Romanò, Cecilia
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Linclau, Bruno
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Reichardt, Niels C.
00b4a72e-ca65-4ea8-a28c-deb3d8ec65fd
Oscarson, Stefan
3b522978-92b1-4b36-8030-54a8615bb33f
Ardá, Ana
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Jiménez-Barbero, Jesús
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Cañada, F. Javier
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Martínez, J. Daniel, Valverde, Pablo, Delgado, Sandra, Romanò, Cecilia, Linclau, Bruno, Reichardt, Niels C., Oscarson, Stefan, Ardá, Ana, Jiménez-Barbero, Jesús and Cañada, F. Javier (2019) Unraveling sugar binding modes to DC-SIGN by employing fluorinated carbohydrates. Molecules. (doi:10.3390/molecules24122337).

Record type: Article

Abstract

A 19F-NMR-based method is employed to assess the binding preferences and interaction details of a library of synthetic fluorinated monosaccharides towards DC-SIGN, a lectin of biomedical interest, which is involved in different viral infections, including HIV and Ebola, and is able to recognize a variety of self- and non-self-glycans. The employed strategy allows not only to screen a mixture of compounds, but also to obtain valuable information on the specific sugar-protein interactions. The analysis of the data demonstrates that monosaccharides Fuc, Man, Glc and Gal are able to bind DC-SIGN, although with decreasing affinity. Moreover, a new binding mode between Man moieties and DC-SIGN, which might have biological implications, has also been detected for the first time. The combination of the 19F with standard 1H-STD-NMR data, assisted by MD simulations, permitted to successfully define this new binding epitope, in which Man coordinates a Ca2+ ion of the lectin CRD through the axial OH-2 and equatorial OH-3 groups, thus mimicking the Fuc/DC-SIGN binding architecture.

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molecules-24-02337 - Version of Record
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Accepted/In Press date: 23 June 2019
Published date: 25 June 2019
Keywords: NMR, molecular recognition, lectin, glycomimetics, DC-SIGN, C-type lectins, fluorinated sugars, 19F-NMR, screening, molecular dynamics

Identifiers

Local EPrints ID: 432115
URI: http://eprints.soton.ac.uk/id/eprint/432115
ISSN: 1420-3049
PURE UUID: d2ea6c52-37b0-442a-9e3c-f1688a71776e
ORCID for Bruno Linclau: ORCID iD orcid.org/0000-0001-8762-0170

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Date deposited: 02 Jul 2019 16:30
Last modified: 16 Mar 2024 03:15

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Contributors

Author: J. Daniel Martínez
Author: Pablo Valverde
Author: Sandra Delgado
Author: Cecilia Romanò
Author: Bruno Linclau ORCID iD
Author: Niels C. Reichardt
Author: Stefan Oscarson
Author: Ana Ardá
Author: Jesús Jiménez-Barbero
Author: F. Javier Cañada

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