Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers
The interaction of multi-LacNAc (Galβ1-4GlcNAc)-containing <i>N</i>-(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-micro...
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doaj-0e97401a1d69496786418cab96a3933f2021-06-30T23:04:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-01226000600010.3390/ijms22116000Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA CopolymersSara Bertuzzi0Ana Gimeno1Ane Martinez-Castillo2Marta G. Lete3Sandra Delgado4Cristina Airoldi5Marina Rodrigues Tavares6Markéta Bláhová7Petr Chytil8Vladimír Křen9Nicola G. A. Abrescia10Ana Ardá11Pavla Bojarová12Jesús Jiménez-Barbero13CIC bioGUNE, Basque Research and Technology Alliance, BRTA, Bizkaia Technology Park, 48162 Derio, Bizkaia, SpainCIC bioGUNE, Basque Research and Technology Alliance, BRTA, Bizkaia Technology Park, 48162 Derio, Bizkaia, SpainCIC bioGUNE, Basque Research and Technology Alliance, BRTA, Bizkaia Technology Park, 48162 Derio, Bizkaia, SpainCIC bioGUNE, Basque Research and Technology Alliance, BRTA, Bizkaia Technology Park, 48162 Derio, Bizkaia, SpainCIC bioGUNE, Basque Research and Technology Alliance, BRTA, Bizkaia Technology Park, 48162 Derio, Bizkaia, SpainBioOrgNMR Lab, Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, ItalyInstitute of Macromolecular Chemistry of the Czech Academy of Sciences, Heyrovského Nám. 2, 16206 Prague, Czech RepublicInstitute of Macromolecular Chemistry of the Czech Academy of Sciences, Heyrovského Nám. 2, 16206 Prague, Czech RepublicInstitute of Macromolecular Chemistry of the Czech Academy of Sciences, Heyrovského Nám. 2, 16206 Prague, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague, Czech RepublicCIC bioGUNE, Basque Research and Technology Alliance, BRTA, Bizkaia Technology Park, 48162 Derio, Bizkaia, SpainCIC bioGUNE, Basque Research and Technology Alliance, BRTA, Bizkaia Technology Park, 48162 Derio, Bizkaia, SpainInstitute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague, Czech RepublicCIC bioGUNE, Basque Research and Technology Alliance, BRTA, Bizkaia Technology Park, 48162 Derio, Bizkaia, SpainThe interaction of multi-LacNAc (Galβ1-4GlcNAc)-containing <i>N</i>-(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.https://www.mdpi.com/1422-0067/22/11/6000galectinmultivalencyglycomimeticmolecular recognitionHPMA copolymerinhibition |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sara Bertuzzi 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 Jesús Jiménez-Barbero |
spellingShingle |
Sara Bertuzzi 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 Jesús Jiménez-Barbero Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers International Journal of Molecular Sciences galectin multivalency glycomimetic molecular recognition HPMA copolymer inhibition |
author_facet |
Sara Bertuzzi 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 Jesús Jiménez-Barbero |
author_sort |
Sara Bertuzzi |
title |
Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers |
title_short |
Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers |
title_full |
Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers |
title_fullStr |
Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers |
title_full_unstemmed |
Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers |
title_sort |
cross-linking effects dictate the preference of galectins to bind lacnac-decorated hpma copolymers |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-06-01 |
description |
The interaction of multi-LacNAc (Galβ1-4GlcNAc)-containing <i>N</i>-(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. |
topic |
galectin multivalency glycomimetic molecular recognition HPMA copolymer inhibition |
url |
https://www.mdpi.com/1422-0067/22/11/6000 |
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