2024-03-28T10:56:05Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1850612021-12-27T16:26:00Zcom_10261_86com_10261_1col_10261_339
Unraveling sugar binding modes to DC-SIGN by employing fluorinated carbohydrates
Martínez, J. Daniel
Valverde Vaquero, Pablo María
Delgado, Sandra
Romanò, Cecilia
Linclau, Bruno
Reichardt, Niels C.
Oscarson, Stefan
Ardá, Ana
Jiménez-Barbero, Jesús
Cañada, F. Javier
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Agencia Estatal de Investigación (España)
European Commission
NMR
Molecular recognition
Lectin
Glycomimetics
DC-SIGN
C-type lectins
Fluorinated sugars
19F-NMR
Screening
Molecular dynamics
17 p.-10 fig.-1 tab.
A fluorine nuclear magnetic resonance (19F-NMR)-based method is employed to assess the binding preferences and interaction details of a library of synthetic fluorinated monosaccharides towards dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (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 strategy employed allows not only screening of a mixture of compounds, but also obtaining 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, is also detected for the first time. The combination of the 19F with standard proton saturation transfer difference (1H-STD-NMR) data, assisted by molecular dynamics (MD) simulations, permits us to successfully define this new binding epitope, where Man coordinates a Ca2+ ion of the lectin carbohydrate recognition domain (CRD) through the axial OH-2 and equatorial OH-3 groups, thus mimicking the Fuc/DC-SIGN binding architecture
2019-06-28T06:42:25Z
2019-06-28T06:42:25Z
2019-06-25
2019-06-28T06:42:26Z
artículo
Molecules 24 (12) 2337 (2019)
1420-3049
http://hdl.handle.net/10261/185061
10.3390/molecules24122337
1420-3049
http://dx.doi.org/10.13039/501100011033
http://dx.doi.org/10.13039/501100000780
31242623
Publisher’s version
https://doi.org/10.3390/molecules24122337
Sí
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2015-64597-C2-1-P
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2015-68756-R
info:eu-repo/grantAgreement/EC/H2020/788143
http://creativecommons.org/licenses/by/4.0/
openAccess
Multidisciplinary Digital Publishing Institute