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Covalent conjugation of allergens to toll-like receptor (TLR) agonists appears to be a powerful strategy for the development of safety compounds for allergen-specific immunomodulatory response toward tolerance in allergy. In this work, we have synthesized two family of ligands, an 8-oxoadenine derivative as a ligand for TLR7 and a pyrimido[5,4-b]indole as a ligand for TLR4, both conjugated with a T-cell peptide of Pru p 3 allergen, the lipid transfer protein (LTP) responsible for LTP-dependent food allergy. These conjugates interact with dendritic cells, inducing their specific maturation, T-cell proliferation, and cytokine production in peach allergic patients. Moreover, they increased the Treg-cell frequencies in these patients and could induce the IL-10 production. These outcomes were remarkable in the case of the TLR7 ligand conjugated with Pru p 3, opening the door for the potential application of these allergen-adjuvant systems in food allergy immunotherapy.

International audience; Chondroitin sulfate type-E (CS-E) is a sulfated polysaccharide that shows several interesting biological activities, such as modulation of the neuronal growth factor signaling and its interaction with langerin, a C-type lectin with a crucial role in the immunological system. However, applications of CS-E are hampered by the typical heterogeneous structure of the natural polysaccharide. Well-defined, homogeneous CS-E analogues are highly demanded. Here, we report the synthesis of monodispersed, structurally well-defined second-generation glycodendrimers displaying up to 18 CS-E disaccharide units. These complex multivalent systems have a molecular weight and a number of disaccharide repeating units comparable with those of the natural polysaccharides. In addition, surface plasmon resonance experiments revealed a calcium-independent interaction between these glycodendrimers and langerin, in the micromolar range, highlighting the utility of these compounds as CS-E mimetics.

The synthesis of multivalent systems based on hexakis-adducts of [60]fullerene employing a biocompatible copper-free click chemistry strategy has been accomplished. A symmetric hexakis-adduct of fullerene bearing 12 maleimide units (3) is reported, and it has been employed to carry out the thiol-maleimide Michael addition. To achieve orthogonal click addition, an asymmetric derivative bearing one maleimide and 10 cyclooctynes has been synthesized. The sequential and one-pot transformations of the two clickable groups have been explored, finding the best results in the case of the one-pot experiment. This route has been used to obtain a biocompatible hexakis-adduct appended with two different biomolecules, carbohydrates, and amino acids.

SWCNTs, MWCNTs, and SWCNHs have been employed as virus-mimicking nanocarbon platforms for the multivalent presentation of carbohydrates in an artificial Ebola virus infection model assay. These carbon nanoforms have been chemically modified by the covalent attachment of glycodendrons and glycofullerenes using the CuAAC >click chemistry> approach. This modification dramatically increases the water solubility of these structurally different nanocarbons. Their efficiency in blocking DC-SIGN-mediated viral infection by an artificial Ebola virus has been tested in a cellular experimental assay, finding that glycoconjugates based on MWCNTs functionalized with glycofullerenes are potent inhibitors of viral infection., Financial support by the European Research Council (ERC-320441-Chirallcarbon), Ministerio de Economı́a y Competitividad (MINECO) of Spain (projects CTQ2017-83531-R, CTQ2017-84327-P, CTQ2017-86265-P, and CTQ2014-52328-P), the Comunidad Autónoma de Madrid (PHOTOCARBON project S2013/MIT-2841), and Instituto de Salud Carlos III (ISCIII) (FIS1400708 and Red de Investigación en SIDA, RIS, RD12/0017) is acknowledged. MICIU/ICTI2017-2020/CTQ2017-84327-P MICIU/ICTI2017-2020/CTQ2017-86265-P MINECO/ICTI2013-2016/CTQ2014-52328-P S2013/MIT-2841/PHOTOCARBON

Glycodendrons bearing nine copies of mannoses or fucoses have been prepared by an efficient convergent strategy based on Cu(I) catalyzed azide−alkyne cycloaddition (CuAAC). These glycodendrons present a well-defined structure and have an adequate size and shape to interact efficiently with the C-type lectin DCSIGN. We have selected a BODIPY derivative to label these glycodendrons due to its interesting physical and chemical properties as chromophore. These BODIPY-labeled glycodendrons were internalized into dendritic cells by mean of DC-SIGN. The internalized mannosylated and fucosylated dendrons are colocalized with LAMP1, which suggests routing to lysosomes. The interaction of these glycodendrons with DC-SIGN at the surface of dendritic cells did not induce maturation of the cells. Signaling analysis by checking different cytokines indicated also the lack of induction the expression of inflammatory and noninflamatory cytokines by these second generation glycodendrons., We would like to acknowledge the financial support by the MICINN of Spain CTQ2008-01694, CTQ2010-20303 and CTQ2011-23410/BQU, the EU RTN CARMUSYS (PITNGA- 2008-213592), and the European FEDER funds. J.J.G.-V. was supported by VENI NWO-ALW (Grant 863.08.020) and Astma Fonds (3.2.10.040).

Three new amphiphilic dendrofullerenes endowed with 4, 8, and 16 carboxylic groups have been efficiently prepared by using a click chemistry methodology. These amphiphilic fullerene derivatives aggregate forming micelles, nanorods, or hollow vesicles depending on the concentration and on the solid substrate., Financial support by the MICINN of Spain (CTQ2008-00795/BQU, CTQ2008-01694), the CAM (MADRISOLAR-2 S2009/PPQ-1533), and Consolider-Ingenio CSD2007-00010, Nanociencia Molecular), and the EU (FUNMOL FP7-212942-1) is greatly appreciated. A.M. thanks the MICINN for an FPI Studentship. This Communication is dedicated to the memory of Prof. Rafael Suau.

3 páginas, 5 figuras., Thiolated self-assembled monolayers of carbohydrates may serve as useful polyvalent tools to mimic the organized presentation of such molecules at the cell surface. SAMs presenting the disaccharide maltose as a neoglycoconjugate were produced, and the structure was studied by high resolution atomic force microscopy. The molecules form highly ordered structures on a gold (111) surface, with lattice parameters determined by the linker moiety rather than the headgroup., This work was supported by the Spanish Ministerio de Educación y Ciencia (Acción Integrada HF2002-0121 and Project No. BQU02-03734) and the French Ministère des Affaires Etrangères (Programme d'Actions Intégrées PICASSO). P.E. thanks the MEC for financial support.