The study of complex multivalent carbohydrate-protein interactions remains highly complicated and sometimes rendered impossible due to aggregation problems. In this study, we demonstrate that bio-layer interferometry is an excellent complementary method to standard techniques such as SPR and ITC. Using tetra- and hexadecavalent GalNAc glycoconjugates and Helix pomatia agglutinin (HPA) as a model lectin, we were able to measure reliable kinetic and thermodynamic parameters of multivalent interactions going from the micro to the nanomolar range.
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http://dx.doi.org/10.1039/c8ob01664j | DOI Listing |
JACS Au
November 2024
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, United Kingdom.
Carbohydrates play pivotal roles in the first stages of microbial infections and can be exploited as decoys to hijack the interactions between bacteria and the host cell. Multivalent glycan probes mimicking the natural presentation of glycans in living cells have been successfully employed to study fundamental carbohydrate/protein interactions in microbial systems; however, most pathogenic glycan receptors exhibit a shared specificity for commonly found sugars present in both healthy and pathogenic cells, posing a challenge for target selectivity. In this study, we report the synthesis of a small library of d-arabinose multivalent probes, a sugar absent in human physiology, and their evaluation in a bacteria agglutination assay using cluster analysis.
View Article and Find Full Text PDFJACS Au
June 2024
Department of Chemistry, University of York, York, YO10 5DD, United Kingdom.
Biofilm formation is integral to the pathogenesis of numerous adherent bacteria and contributes to antimicrobial resistance (AMR). The rising threat of AMR means the need to develop novel nonbactericidal antiadhesion approaches against such bacteria is more urgent than ever. Both adherent-invasive (AIEC, implicated in inflammatory bowel disease) and uropathogenic (UPEC, responsible for ∼80% of urinary tract infections) adhere to terminal mannose sugars on epithelial glycoproteins through the FimH adhesin on their type 1 pilus.
View Article and Find Full Text PDFACS Cent Sci
November 2023
Department of Medicine, McMaster Immunology Research Center, Center for Discovery in Cancer Research, Department of Biochemistry and Biomedical Sciences, and Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton Ontario, Canada.
Carbohydrate-binding receptors are often used by the innate immune system to potentiate inflammation, target endocytosis/destruction, and adaptive immunity (e.g., CD206, DC-SIGN, MBL, and anticarbohydrate antibodies).
View Article and Find Full Text PDFBioconjug Chem
January 2024
Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Plz. Ramón y Cajal s/n, Madrid, C.P. 28040, España.
Multivalent glycodendrimers are valuable tools for studying carbohydrate-protein interactions, and their scaffolds represent important components to increase specificity and affinity. Previous work by our group described the preparation of a tetravalent glucuronic acid rigid dendron that binds with good affinity to the dengue virus envelope protein ( = 22 μM). Herein, the chemical synthesis and binding analysis of three new sets of rigid, semirigid, and flexible glucuronic acid-based dendrimers bearing different levels of multivalency and their interactions with the dengue virus envelope protein are described.
View Article and Find Full Text PDFBioorg Chem
December 2023
Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Plz. Ramón y Cajal s/n, Madrid C.P. 28040, Spain. Electronic address:
Multivalent glycodendrons are valuable tools to mimic many structural and functional features of cell-surface glycoconjugates and its focal position scaffolds represent important components to increase specificity and affinity. Previous work in our group described the preparation of a tetravalent glucuronic acid dendron that binds with good affinity to Dengue virus envelope protein (K = 22 μM). Herein, the chemical synthesis and binding analysis of a new library of potent glucuronic acid dendrons bearing different functional group at the focal position and different level of multivalency are described.
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