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Glycofullerenes Inhibit Viral Infection

Authors: Joanna Luczkowiak, Antonio Muñoz, Macarena Sánchez-Navarro, Renato Ribeiro-Viana, Anthony Ginieis, Beatriz M. Illescas, Nazario Martín, Rafael Delgado, Javier Rojo
Journal reference: Biomacromolecules 2013, 14, 431−434; DOI: 10.1021/bm3016658

 

Abstract
Water-soluble glycofullerenes based on a hexakis-adduct of [60]fullerene with an octahedral addition pattern are very attractive compounds providing a spherical presentation of carbohydrates. These tools have been recently described and they have been used to interact with lectins in a multivalent manner. Here, we present the use of these glycofullerenes, including new members with 36 mannoses, as compounds able to inhibit a DC-SIGN-dependent cell infection by pseudotyped viral particles. The results obtained in these experiments demonstrate for the first time that these glycoconjugates are adequate to inhibit efficiently an infection process, and therefore, they can be considered as very promising and interesting tools to interfere in biological events where lectins such as DC-SIGN are involved.

Chemoenzymatic Synthesis of O-Mannosylpeptides in Solution and on Solid Phase

Authors: Robert Šardzík, Anthony P. Green, Nicolas Laurent, Peter Both, Carolina Fontana, Josef Voglmeir, Martin J. Weissenborn, Rose Haddoub, Paola Grassi, Stuart M. Haslam, Göran Widmalm, and Sabine L. Flitsch

Journal reference: J. Am. Chem. Soc., 2012, 134 (10), pp 4521–4524
DOI: 10.1021/ja211861m

 

Abstract
O-Mannosyl glycans are known to play an important role in regulating the function of α-dystroglycan (α-DG), as defective glycosylation is associated with various phenotypes of congenital muscular dystrophy. Despite the well-established biological significance of these glycans, questions regarding their precise molecular function remain unanswered. Further biological investigation will require synthetic methods for the generation of pure samples of homogeneous glycopeptides with diverse sequences. Here we describe the first total syntheses of glycopeptides containing the tetrasaccharide NeuNAcα2-3Galβ1-4GlcNAcβ1-2Manα, which is reported to be the most abundant O-mannosyl glycan on α-DG. Our approach is based on biomimetic stepwise assembly from the reducing end and also gives access to the naturally occurring mono-, di-, and trisaccharide substructures. In addition to the total synthesis, we have developed a “one-pot” enzymatic cascade leading to the rapid synthesis of the target tetrasaccharide. Finally, solid-phase synthesis of the desired glycopeptides directly on a gold microarray platform is described.

Virus-like glycodendrinanoparticles displaying quasi-equivalent nested polyvalency upon glycoprotein platforms potently block viral infection

Authors: Renato Ribeiro-Viana, Macarena Sánchez-Navarro, Joanna Luczkowiak, Julia R. Koeppe, Rafael Delgado, Javier Rojo, Benjamin G. Davis.

Journal: Nature Communications 2012 DOI: 10.1038/ncomms2302

 

Abstract Ligand polyvalency is a powerful modulator of protein– receptor interactions. Host–pathogen infection interactions are often mediated by glycan ligand–protein interactions, yet its interrogation with very high copy number ligands has been limited to heterogenous systems. Here we report that through the use of nested layers of multivalency we are able to assemble the most highly valent glycodendrimeric constructs yet seen (bearing up to 1,620 glycans). These constructs are pure and well-defined single entities that at diameters of up to 32nm are capable of mimicking pathogens both in size and in their highly glycosylated surfaces. Through this mimicry these glyco-dendri-protein-nano-particles are capable of blocking (at picomolar concentrations) a model of the infection of T- lymphocytes and human dendritic cells by Ebola virus. The high associated polyvalency effects (B>106, B/N ≈102–103) displayed on an unprecedented surface area by precise clusters suggest a general strategy for modulation of such interactions.