Insights into Molecular Recognition of LewisX Mimics by DC-SIGN Using NMR and Molecular Modelling
Articolo
Data di Pubblicazione:
2011
Citazione:
Insights into Molecular Recognition of LewisX Mimics by DC-SIGN Using NMR and Molecular Modelling / C. Guzzi, J. Angulo, F. Doro, J.J. Reina, M. Thépaut, F. Fieschi, A. Bernardi, J. Rojo, P.M. Nieto. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - 9:22(2011 Oct), pp. 7705-7712.
Abstract:
In this work, we have studied in detail the binding of two a-fucosylamide-based mimics of LewisX to
DC-SIGN ECD (ECD = extracellular domain) using STD NMR and docking. We have concluded that
the binding mode occurs mainly through the fucose moiety, in the same way as LewisX. Similarly to
other mimics containing mannose or fucose previously studied, we have shown that both compounds
bind to DC-SIGN ECD in a multimodal fashion. In this case, the main contact is the interaction of two
hydroxyl groups one equatorial and the other one axial (O3 and O4) of the fucose with the Ca2+ as
LewisX and similarly to mannose-containing mimics (in this case the interacting groups are both in the
equatorial position). Finally, we have measured the KD of one mimic that was 0.4 mM. Competitive
STD NMR experiments indicate that the aromatic moiety provides additional binding contacts that
increase the affinity.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
carbohydrates ; glycomimetics ; NMR ; lectins ; DC-SIGN
Elenco autori:
C. Guzzi, J. Angulo, F. Doro, J.J. Reina, M. Thépaut, F. Fieschi, A. Bernardi, J. Rojo, P.M. Nieto
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