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High-affinity N-(2-hydroxypropyl)methacrylamide copolymers with tailored N-acetyllactosamine presentation discriminate between galectins
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SYSNO ASEP 0521956 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title High-affinity N-(2-hydroxypropyl)methacrylamide copolymers with tailored N-acetyllactosamine presentation discriminate between galectins Author(s) Tavares, Marina Rodrigues (UMCH-V) ORCID, RID
Bláhová, Markéta (UMCH-V) RID, ORCID
Sedláková, Lieselotte (MBU-M)
Elling, L. (DE)
Pelantová, Helena (MBU-M) ORCID, RID
Konefal, Rafal (UMCH-V) RID, ORCID
Etrych, Tomáš (UMCH-V) RID, ORCID
Křen, Vladimír (MBU-M) RID, ORCID
Bojarová, Pavla (MBU-M) ORCID
Chytil, Petr (UMCH-V) RID, ORCIDSource Title Biomacromolecules. - : American Chemical Society - ISSN 1525-7797
Roč. 21, č. 2 (2020), s. 641-652Number of pages 12 s. Language eng - English Country US - United States Keywords HPMA copolymers ; drug delivery systems ; galectines Subject RIV CD - Macromolecular Chemistry OECD category Polymer science Subject RIV - cooperation Institute of Microbiology - Macromolecular Chemistry R&D Projects LTC17005 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LTC19038 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GA18-01163S GA ČR - Czech Science Foundation (CSF) GA17-13721S GA ČR - Czech Science Foundation (CSF) GA19-01417S GA ČR - Czech Science Foundation (CSF) LO1507 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support UMCH-V - RVO:61389013 ; MBU-M - RVO:61388971 UT WOS 000513091100036 EID SCOPUS 85079203166 DOI 10.1021/acs.biomac.9b01370 Annotation N-Acetyllactosamine (LacNAc, Galβ4GlcNAc) is a typical disaccharide ligand of galectins. The most abundant members of these human lectins, galectin-1 (Gal-1) and galectin-3 (Gal-3), participate in a number of pathologies including cancerogenesis and metastatic formation. In this study, we synthesized a series of fifteen N-(2-hydroxypropyl)methacrylamide (HPMA)-based glycopolymers with varying LacNAc amounts and presentations and evaluated the impact of their architecture on the binding affinity to Gal-1 and Gal-3. The controlled radical reversible addition–fragmentation chain transfer copolymerization technique afforded linear polymer precursors with comparable molecular weight (Mn ≈ 22,000 g mol–1) and narrow dispersity (D̵ ≈ 1.1). The precursors were conjugated with the functionalized LacNAc disaccharide (4–22 mol % content in glycopolymer) prepared by enzymatic synthesis under catalysis by β-galactosidase from Bacillus circulans. The structure–affinity relationship study based on the enzyme-linked immunosorbent assay revealed that the type of LacNAc presentation, individual or clustered on bi- or trivalent linkers, brings a clear discrimination (almost 300-fold) between Gal-1 and Gal-3, reaching avidity to Gal-1 in the nanomolar range. Whereas Gal-1 strongly preferred a dense presentation of individually distributed LacNAc epitopes, Gal-3 preferred a clustered LacNAc presentation. Such a strong galectin preference based just on the structure of a multivalent glycopolymer type is exceptional. The prepared nontoxic, nonimmunogenic, and biocompatible glycopolymers are prospective for therapeutic applications requiring selectivity for one particular galectin. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2021 Electronic address https://pubs.acs.org/doi/10.1021/acs.biomac.9b01370
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