The efficient synthesis of fluorescent and non-fluorescent multivalent neoglycoconjugates is described by means of the Cu(i) catalyzed azide-alkyne 1,3-dipolar cycloaddition ("click-chemistry"). A well-defined glycopolymer, glycocyclodextrin or glycocluster architecture displaying galactose or lactose epitopes has been chosen. Cellular assays using U-937 and RAW 264.7 monocyte/macrophage cells showed that these glycocompounds have the capability to act as synthetic activators mimicking the lipopolysaccharide (LPS) effects. Thus, the click compounds promote cell adhesion and stimulation of monocytes, measured as an increase in the amount of TNFalpha, facilitating their differentiation to macrophages.
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http://dx.doi.org/10.1039/b706331h | DOI Listing |
Carbohydr Res
June 2021
School of Chemical Engineering, Nanjing University of Science & Technology, Nanjing, Jiangsu, 210094, PR China. Electronic address:
Polyhydroxylated alkaloids display a wide range of biological activities, suggesting their use in the treatment of various diseases. Their most famous representative, 1-deoxynojirimycin (DNJ), is a natural product that shows α- and β-glucosidase inhibition. This molecule has been since converted into two clinically approved drugs i.
View Article and Find Full Text PDFBioconjug Chem
March 2019
Université Grenoble Alpes, CNRS, CERMAV , 38000 Grenoble , France.
The approach developed here offers a straightforward and efficient access to β- C-glycosyl barbiturate ligands, spanning from glycomimetics to multivalent C-neoglycoconjugates, with the aim of deciphering structural parameters impacting the binding to pathogenic lectins. We reinvestigated the Knoevenagel condensation of barbituratic acid on protecting-group free carbohydrates and successfully designed sodium and 5,5-disubstituted N, N-dimethyl barbiturate forms of D-galactose, L-fucose, melibiose, 2'-fucosyllactose, and maltose and evaluated their binding affinity by isothermal titration calorimetry with LecA (galactose-binding lectin) and LecB (fucose-binding lectin) from Pseudomonas aeruginosa and RSL (fucose-binding lectin) from Ralstonia solanacearum. The barbiturate ring was shown to be detrimental for binding to LecA ( K in mM range) and even more to LecB (noninteraction) while RSL is much more tolerant especially in the presence of an aromatic group ( K in μM range).
View Article and Find Full Text PDFBioconjug Chem
January 2019
Faculty of Health Sciences and Department of Molecular Biology and Biochemistry , Simon Fraser University , 8888 University Drive, Burnaby , British Columbia V5A1S6 , Canada.
Novel neoglycoproteins containing oligomannosidic penta- and heptasaccharides as structural variants of oligomannose-type N-glycans found on human immunodeficiency virus type 1 gp120 have been prepared using different conjugation methods. Two series of synthetic ligands equipped with 3-aminopropyl spacer moieties and differing in the anomeric configuration of the reducing mannose residue were activated either as isothiocyanates or as adipic acid succinimidoyl esters and coupled to bovine serum albumin. Coupling efficiency for adipic acid connected neoglycoconjugates was better than for the thiourea-linked derivatives; the latter constructs, however, exhibited higher reactivity toward antibody 2G12, an HIV-neutralizing antibody with exquisite specificity for oligomannose-type glycans.
View Article and Find Full Text PDFBioconjug Chem
October 2018
CNRS, UMR 7244, CSPBAT, Laboratoire de Chimie, Structures et Propriétés de Biomateriaux et d'Agents Therapeutiques , Université Paris 13, Sorbonne Paris Cité , 93000 Bobigny , France.
Galectins (Gal) are a family of glycan-binding proteins characterized by their affinity for β-galactosides. Galectin-1 (Gal-1), a dimeric lectin with two galactoside-binding sites, regulates cancer progression and immune responses. Coordination chemistry has been engaged to develop versatile multivalent neoglycoconjugates for binding Gal-1.
View Article and Find Full Text PDFBeilstein J Org Chem
November 2014
Dipartimento di Chimica and ISTM-CNR, Universita degli Studi di Milano, via Golgi 19, I-20133 Milano, Italy.
A vaccine to prevent infections from the emerging Neisseria meningitidis X (MenX) is becoming an urgent issue. Recently MenX capsular polysaccharide (CPS) fragments conjugated to CRM197 as carrier protein have been confirmed at preclinical stage as promising candidates for vaccine development. However, more insights about the minimal epitope required for the immunological activity of MenX CPS are needed.
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