Publications (9) View all
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Dataset: Thepaut et al (2013) sup info
Michel Thépaut, Cinzia Guzzi, Ieva Sutkeviciute, Sara Sattin, Renato Ribeiro-Viana, Norbert Varga, Eric Chabrol, Javier Rojo, Anna Bernardi, Jesús Angulo, Pedro M Nieto, Franck Fieschi -
SourceAvailable from: Franck Fieschi
Article: Structure of a glycomimetic ligand in the Carbohydrate Recognition Domain of C-type lectin DC-SIGN. Structural requirements for selectivity and ligand design.
Michel Thépaut, Cinzia Guzzi, Ieva Sutkeviciute, Sara Sattin, Renato Ribeiro-Viana, Norbert Varga, Eric Chabrol, Javier Rojo, Anna Bernardi, Jesús Angulo, Pedro M Nieto, Franck Fieschi[show abstract] [hide abstract]
ABSTRACT: In genital mucosa, different fates are described for HIV according to the sub-type of dendritic cells (DCs) involved in its recognition. This notably depends on the C-type lectin receptor, langerin or DC-SIGN, involved in gp120 interaction. Langerin blocks HIV transmission by its internalization in specific organelles of Langerhans cells. On the contrary DC-SIGN enhances HIV trans-infection of T lymphocytes. Thus, approaches aiming to inhibit DC-SIGN, without blocking langerin, represent attractive anti-HIV strategies. We previously demonstrated that dendrons bearing multiple copies of glycomimetic compounds were able to block DC-SIGN-dependent HIV infection in cervical explant models. Optimization of such ligand requires detailed characterization of its binding mode. In the present work we determined the first high-resolution structure of a glycomimetic/DC-SIGN complex by X-ray crystallography. This glycomimetic, pseudo-1,2-mannobioside, shares shape and conformational properties with Manα1-2Man, its natural counterpart. However, it uses the binding epitope previously described for Lewis X, a ligand specific for DC-SIGN among the C-type lectin family. Thus, selectivity gain for DC-SIGN vs langerin is observed with pseudo-1,2-mannobioside as shown by surface plasmon resonance analysis. In parallel, ligand binding was also analyzed by TR-NOESY and STD NMR experiments, combined with the CORCEMA-ST protocol. These studies demonstrate that the complex, defined by X-ray crystallography, represents the unique binding mode of this ligand as opposed to the several binding orientations described for the natural ligand. This exclusive binding mode and its selective interaction properties position this glycomimetic as a good lead compound for rational improvement based on a structurally driven approach.Journal of the American Chemical Society 01/2013; · 9.91 Impact Factor -
SourceAvailable from: Marko Anderluh
Dataset: Obermajer et al
Michela Bruno, Nataša Obermajer, Urban Svajger, Marko Anderluh, Sara Sattin, Anna Bernardi, Cinzia Colombo -
SourceAvailable from: Sara Sattin
Article: Giant regular polyhedra from calixarene carboxylates and uranyl.
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ABSTRACT: Self-assembly of large multi-component systems is a common strategy for the bottom-up construction of discrete, well-defined, nanoscopic-sized cages. Icosahedral or pseudospherical viral capsids, built up from hundreds of identical proteins, constitute typical examples of the complexity attained by biological self-assembly. Chemical versions of the so-called 5 Platonic regular or 13 Archimedean semi-regular polyhedra are usually assembled combining molecular platforms with metals with commensurate coordination spheres. Here we report novel, self-assembled cages, using the conical-shaped carboxylic acid derivatives of calix[4]arene and calix[5]arene as ligands, and the uranyl cation UO(2)2+ as a metallic counterpart, which coordinates with three carboxylates at the equatorial plane, giving rise to hexagonal bipyramidal architectures. As a result, octahedral and icosahedral anionic metallocages of nanoscopic dimensions are formed with an unusually small number of components.Nature Communications 01/2012; 3:785. · 7.40 Impact Factor -
SourceAvailable from: Franck Fieschi
Article: Pseudosaccharide functionalized dendrimers as potent inhibitors of DC-SIGN dependent Ebola pseudotyped viral infection.
Joanna Luczkowiak, Sara Sattin, Ieva Sutkevičiūtė, José Juan Reina, Macarena Sánchez-Navarro, Michel Thépaut, Lorena Martínez-Prats, Anna Daghetti, Franck Fieschi, Rafael Delgado, Anna Bernardi, Javier Rojo[show abstract] [hide abstract]
ABSTRACT: The development of compounds with strong affinity for the receptor DC-SIGN is a topic of remarkable interest due to the role that this lectin plays in several pathogen infection processes and in the modulation of the immune response. DC-SIGN recognizes mannosylated and fucosylated oligosaccharides in a multivalent manner. Therefore, multivalent carbohydrate systems are required to interact in an efficient manner with this receptor and compete with the natural ligands. We have previously demonstrated that linear pseudodi- and pseudotrisaccharides are adequate ligands for DC-SIGN. In this work, we show that multivalent presentations of these glycomimetics based on polyester dendrons and dendrimers lead to very potent inhibitors (in the nanomolar range) of cell infection by Ebola pseudotyped viral particles by blocking DC-SIGN receptor. Furthermore, SPR model experiments confirm that the described multivalent glycomimetic compounds compete in a very efficient manner with polymannosylated ligands for binding to DC-SIGN.Bioconjugate Chemistry 06/2011; 22(7):1354-65. · 4.93 Impact Factor