Publications by authors named "Silvia Mari"

35 Publications

1,2-Mannobioside mimic: synthesis, DC-SIGN interaction by NMR and docking, and antiviral activity.

ChemMedChem 2007 Jul;2(7):1030-6

Departamento de Química Bioorgánica, Instituto de Investigaciones Químicas, CSIC, Américo Vespucio 49, 41092 Sevilla, Spain.

The design and preparation of carbohydrate ligands for DC-SIGN is a topic of high interest because of the role played by this C-type lectin in immunity and infection processes. The low chemical stability of carbohydrates against enzymatic hydrolysis by glycosylases has stimulated the search for new alternatives more stable in vivo. Herein, we present a good alternative for a DC-SIGN ligand based on a mannobioside mimic with a higher enzymatic stability than the corresponding disaccharide. NMR and docking studies have been performed to study the interaction of this mimic with DC-SIGN in solution demonstrating that this pseudomannobioside is a good ligand for this lectin. In vitro studies using an infection model with Ebola pseudotyped virus demonstrates that this compound presents an antiviral activity even better than the corresponding disaccharide and could be an interesting ligand to prepare multivalent systems with higher affinities for DC-SIGN with potential biomedical applications.
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http://dx.doi.org/10.1002/cmdc.200700047DOI Listing
July 2007

Synthesis and conformational analysis of an alpha-D-mannopyranosyl-(1-->2)-alpha-D-mannopyranosyl-(1-->6)-alpha-D-mannopyranose mimic.

Carbohydr Res 2007 Sep 24;342(12-13):1859-68. Epub 2007 Mar 24.

Centro de Investigaciones Biológicas, Departamento de Estructura y Functión de Proteínas, CSIC, c/Ramiro de Maeztu 9, 28040 Madrid, Spain.

A mimic of a (1-->2),(1-->6)-mannotrioside was synthesized by replacing the central mannose unit with an enantiomerically pure, conformationally stable trans-diaxial cyclohexanediol. The three-dimensional structure of the molecule was investigated by NMR spectroscopy supported by molecular modelling and was compared to the known features of the natural mannotrioside.
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http://dx.doi.org/10.1016/j.carres.2007.03.019DOI Listing
September 2007

1D saturation transfer difference NMR experiments on living cells: the DC-SIGN/oligomannose interaction.

Angew Chem Int Ed Engl 2004 Dec;44(2):296-8

Centro de Investigaciones Biológicas, Departamentos de Inmunología y de Estructura de Proteínas, C.S.I.C., c/Ramiro de Maeztu 9, 28040 Madrid, Spain.

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http://dx.doi.org/10.1002/anie.200461574DOI Listing
December 2004

Intramolecular carbohydrate-aromatic interactions and intermolecular van der Waals interactions enhance the molecular recognition ability of GM1 glycomimetics for cholera toxin.

Chemistry 2004 Sep;10(18):4395

Università di Milano-Dipartimento di Chimica Organica e Industriale e Centro di Eccellenza CISI via Venezian 21, 20133 Milano, Italy.

The design and synthesis of two GM1 glycomimetics, 6 and 7, and analysis of their conformation in the free state and when complexed to cholera toxin is described. These compounds, which include an (R)-cyclohexyllactic acid and an (R)-phenyllactic acid fragment, respectively, display significant affinity for cholera toxin. A detailed NMR spectroscopy study of the toxin/glycomimetic complexes, assisted by molecular modeling techniques, has allowed their interactions with the toxin to be explained at the atomic level. It is shown that intramolecular van der Waals and CH-pi carbohydrate-aromatic interactions define the conformational properties of 7, which adopts a three-dimensional structure significantly preorganized for proper interaction with the toxin. The exploitation of this kind of sugar-aromatic interaction, which is very well described in the context of carbohydrate/protein complexes, may open new avenues for the rational design of sugar mimics.
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http://dx.doi.org/10.1002/chem.200400084DOI Listing
September 2004

Mimics of ganglioside GM1 as cholera toxin ligands: replacement of the GalNAc residue.

Org Biomol Chem 2003 Mar;1(5):785-92

Universita' di Milano, Dipartimento di Chimica Organica e Industriale, Centro di Eccellenza CISI, via Venezian 21, 20133 Milano, Italy.

Two new cholera toxin (CT) ligands (4 and 5) are described. The new ligands were designed starting from the known GM1 mimics 2 and 3 by replacement of their GalNAc residue with the C4 isomer GlcNAc. As predicted by molecular modelling, the conformational properties of the equivalent pairs 2-4 and 3-5 are very similar and their affinity for CT is of the same order of magnitude. NMR experiments have also proved that 5 occupies the GM1-binding site of the toxin and have revealed its bound conformation.
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http://dx.doi.org/10.1039/b210503aDOI Listing
March 2003