Počet záznamů: 1
Immunoprotective neo-glycoproteins: Chemoenzymatic synthesis of multivalent glycomimetics for inhibition of cancer-related galectin-3
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SYSNO ASEP 0544083 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Immunoprotective neo-glycoproteins: Chemoenzymatic synthesis of multivalent glycomimetics for inhibition of cancer-related galectin-3 Tvůrce(i) Heine, Viktoria (MBU-M)
Hovorková, Michaela (MBU-M)
Vlachová, Miluše (MBU-M) ORCID
Filipová, Marcela (UMCH-V) RID, ORCID
Bumba, Ladislav (MBU-M) RID, ORCID
Janoušková, Olga (UMCH-V) RID, SAI, ORCID
Hubálek, Martin (UOCHB-X) RID, ORCID
Cvačka, Josef (UOCHB-X) RID, ORCID
Petrásková, Lucie (MBU-M) ORCID
Pelantová, Helena (MBU-M) ORCID, RID
Křen, Vladimír (MBU-M) RID, ORCID
Elling, L. (DE)
Bojarová, Pavla (MBU-M) ORCIDČíslo článku 113500 Zdroj.dok. European Journal of Medicinal Chemistry. - : Elsevier - ISSN 0223-5234
Roč. 220, AUG 5 2021 (2021)Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. FR - Francie Klíč. slova Cancer ; Galectin-3 ; Glycomimetic ; Inhibition ; Neo-glycoprotein Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology Vědní obor RIV – spolupráce Ústav makromolekulární chemie - Makromolekulární chemie
Ústav organické chemie a biochemie - Analytická chemie, separaceCEP GA20-00215S GA ČR - Grantová agentura ČR LTC19038 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LTC18041 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LM2018133 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Omezený přístup Institucionální podpora MBU-M - RVO:61388971 ; UMCH-V - RVO:61389013 ; UOCHB-X - RVO:61388963 UT WOS 000659148800034 EID SCOPUS 85105339936 DOI 10.1016/j.ejmech.2021.113500 Anotace 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. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2022 Elektronická adresa https://www.sciencedirect.com/science/article/pii/S0223523421003494?via%3Dihub
Počet záznamů: 1