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Article

Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers

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CIC bioGUNE, Basque Research and Technology Alliance, BRTA, Bizkaia Technology Park, 48162 Derio, Bizkaia, Spain
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BioOrgNMR Lab, Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
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Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Heyrovského Nám. 2, 16206 Prague, Czech Republic
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Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague, Czech Republic
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Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Bizkaia, Spain
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Department of Health Care Disciplines and Population Protection, Faculty of Biomedical Engineering, Czech Technical University in Prague, Nám. Sítná, 27201 Kladno, Czech Republic
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Department of Organic Chemistry II, University of the Basque Country UPV/EHU, 48940 Leioa, Bizkaia, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Cheorl-Ho Kim
Int. J. Mol. Sci. 2021, 22(11), 6000; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116000
Received: 14 May 2021 / Revised: 28 May 2021 / Accepted: 29 May 2021 / Published: 1 June 2021
(This article belongs to the Special Issue Glycoconjugates and Glycomimetics for Targeting Lectins)
The interaction of multi-LacNAc (Galβ1-4GlcNAc)-containing N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers with human galectin-1 (Gal-1) and the carbohydrate recognition domain (CRD) of human galectin-3 (Gal-3) was analyzed using NMR methods in addition to cryo-electron-microscopy and dynamic light scattering (DLS) experiments. The interaction with individual LacNAc-containing components of the polymer was studied for comparison purposes. For Gal-3 CRD, the NMR data suggest a canonical interaction of the individual small-molecule bi- and trivalent ligands with the lectin binding site and better affinity for the trivalent arrangement due to statistical effects. For the glycopolymers, the interaction was stronger, although no evidence for forming a large supramolecule was obtained. In contrast, for Gal-1, the results indicate the formation of large cross-linked supramolecules in the presence of multivalent LacNAc entities for both the individual building blocks and the polymers. Interestingly, the bivalent and trivalent presentation of LacNAc in the polymer did not produce such an increase, indicating that the multivalency provided by the polymer is sufficient for triggering an efficient binding between the glycopolymer and Gal-1. This hypothesis was further demonstrated by electron microscopy and DLS methods. View Full-Text
Keywords: galectin; multivalency; glycomimetic; molecular recognition; HPMA copolymer; inhibition; glycopolymer galectin; multivalency; glycomimetic; molecular recognition; HPMA copolymer; inhibition; glycopolymer
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MDPI and ACS Style

Bertuzzi, S.; Gimeno, A.; Martinez-Castillo, A.; Lete, M.G.; Delgado, S.; Airoldi, C.; Rodrigues Tavares, M.; Bláhová, M.; Chytil, P.; Křen, V.; Abrescia, N.G.A.; Ardá, A.; Bojarová, P.; Jiménez-Barbero, J. Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers. Int. J. Mol. Sci. 2021, 22, 6000. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116000

AMA Style

Bertuzzi S, Gimeno A, Martinez-Castillo A, Lete MG, Delgado S, Airoldi C, Rodrigues Tavares M, Bláhová M, Chytil P, Křen V, Abrescia NGA, Ardá A, Bojarová P, Jiménez-Barbero J. Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers. International Journal of Molecular Sciences. 2021; 22(11):6000. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116000

Chicago/Turabian Style

Bertuzzi, Sara, Ana Gimeno, Ane Martinez-Castillo, Marta G. Lete, Sandra Delgado, Cristina Airoldi, Marina Rodrigues Tavares, Markéta Bláhová, Petr Chytil, Vladimír Křen, Nicola G.A. Abrescia, Ana Ardá, Pavla Bojarová, and Jesús Jiménez-Barbero. 2021. "Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers" International Journal of Molecular Sciences 22, no. 11: 6000. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116000

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