Issue 22, 2011
From the journal:

Organic & Biomolecular Chemistry

Insights into molecular recognition of LewisX mimics by DC-SIGN using NMR and molecular modelling†

Cinzia Guzzi,a   Jesús Angulo,a   Fabio Doro,b   José J. Reina,b   Michel Thépaut,cde   Franck Fieschi,cdf   Anna Bernardi,b   Javier Rojoa  and  Pedro M. Nieto*a  

* Corresponding authors

a Glycosystems Laboratory, Instituto de Investigaciones Químicas, CSIC-US, AmericoVespucio, 49 41092 Sevilla, Spain
E-mail: pedro.nieto@iiq.csic.es
Fax: +34 954460595
Tel: +34 954489568

b Universita' degli Studi di Milano, Dipartimento di Chimica Organica e Industriale and CISI, via Venezian 21, 20133 Milano, Italy

c Institut de Biologie Structurale, Université Grenoble I, 41 rue Jules Horowitz, 38027 Grenoble, France

d CNRS, UMR 5075 Grenoble, France

e CEA, Grenoble, France

f Institut Universitaire de France, 103 boulevard Saint-Michel, Paris, France

Abstract

In this work, we have studied in detail the binding of two α-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.

Graphical abstract: Insights into molecular recognition of LewisX mimics by DC-SIGN using NMR and molecular modelling

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Article information

DOI
https://doi.org/10.1039/C1OB05938F
Article type
Paper
Submitted
10 Jun 2011
Accepted
31 Aug 2011
First published
01 Sep 2011

Org. Biomol. Chem., 2011,9, 7705-7712

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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 and P. M. Nieto, Org. Biomol. Chem., 2011, 9, 7705 DOI: 10.1039/C1OB05938F

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