Počet záznamů: 1
Immunoprotective neo-glycoproteins: Chemoenzymatic synthesis of multivalent glycomimetics for inhibition of cancer-related galectin-3
- 1.0544083 - MBÚ 2022 RIV FR eng J - Článek v odborném periodiku
Heine, Viktoria - Hovorková, Michaela - Vlachová, Miluše - Filipová, Marcela - Bumba, Ladislav - Janoušková, Olga - Hubálek, Martin - Cvačka, Josef - Petrásková, Lucie - Pelantová, Helena - Křen, Vladimír - Elling, L. - Bojarová, Pavla
Immunoprotective neo-glycoproteins: Chemoenzymatic synthesis of multivalent glycomimetics for inhibition of cancer-related galectin-3.
European Journal of Medicinal Chemistry. Roč. 220, AUG 5 2021 (2021), č. článku 113500. ISSN 0223-5234. E-ISSN 1768-3254
Grant CEP: GA ČR(CZ) GA20-00215S; GA MŠMT(CZ) LTC19038; GA MŠMT(CZ) LTC18041; GA MŠMT(CZ) LM2018133
GRANT EU: European Commission(XE) CA16225
Grant ostatní: AV ČR(CZ) DAAD-20-04
Program: Bilaterální spolupráce
Institucionální podpora: RVO:61388971 ; RVO:61389013 ; RVO:61388963
Klíčová slova: Cancer * Galectin-3 * Glycomimetic * Inhibition * Neo-glycoprotein
Obor OECD: Biochemistry and molecular biology; Polymer science (UMCH-V); Analytical chemistry (UOCHB-X)
Impakt faktor: 7.088, rok: 2021
Způsob publikování: Omezený přístup
https://www.sciencedirect.com/science/article/pii/S0223523421003494?via%3Dihub
Galectin-3 plays a crucial role in cancerogenesis, its targeting is a prospective pathway in cancer diagnostics and therapy. Multivalent presentation of glycans was shown to strongly increase the affinity of glycoconjugates to galectin-3. Further strengthening of interaction with galectin-3 may be accomplished using artificial glycomimetics with apt aryl substitutions. We established a new, as yet undescribed chemoenzymatic method to produce selective C-3-substituted N,N'-diacetyllactosamine glycomimetics and coupled them to human serum albumin. From a library of enzymes, only beta-N-acetylhexosaminidase from Talaromyces flavus was able to efficiently synthesize the C-3-propargylated disaccharide. Various aryl residues were attached to the functionalized N,N'-diacetyllactosamine via click chemistry to assess the impact of the aromatic substitution. In ELISA-type assays with galectin-3, free glycomimetics exhibited up to 43-fold stronger inhibitory potency to Gal-3 than the lactose standard. Coupling to human serum albumin afforded multivalent neo-glycoproteins with up to 4209-fold increased inhibitory potency per glycan compared to the monovalent lactose standard. Surface plasmon resonance brought further information on the kinetics of galectin-3 inhibition. The potential of prepared neo-glycoproteins to target galectin-3 was demonstrated on colorectal adenocarcinoma DLD-1 cells. We investigated the uptake of neo-glycoproteins into cells and observed limited non-specific transport into the cytoplasm. Therefore, neo-glycoproteins primarily act as efficient scavengers of exogenous galectin-3 of cancer cells, inhibiting its interaction with the cell surface, and protecting T-lymphocytes against galectin-3-induced apoptosis. The present neo-glycoproteins combine the advantage of a straightforward synthesis, selectivity, non-toxicity, and high efficiency for targeting exogenous galectin-3.
Trvalý link: http://hdl.handle.net/11104/0321173
Počet záznamů: 1