Cargando…
Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers
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 l...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199549/ https://www.ncbi.nlm.nih.gov/pubmed/34206141 http://dx.doi.org/10.3390/ijms22116000 |
_version_ | 1783707402793648128 |
---|---|
author | Bertuzzi, Sara Gimeno, Ana Martinez-Castillo, Ane Lete, Marta G. Delgado, Sandra Airoldi, Cristina Rodrigues Tavares, Marina Bláhová, Markéta Chytil, Petr Křen, Vladimír Abrescia, Nicola G. A. Ardá, Ana Bojarová, Pavla Jiménez-Barbero, Jesús |
author_facet | Bertuzzi, Sara Gimeno, Ana Martinez-Castillo, Ane Lete, Marta G. Delgado, Sandra Airoldi, Cristina Rodrigues Tavares, Marina Bláhová, Markéta Chytil, Petr Křen, Vladimír Abrescia, Nicola G. A. Ardá, Ana Bojarová, Pavla Jiménez-Barbero, Jesús |
author_sort | Bertuzzi, Sara |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8199549 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81995492021-06-14 Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers Bertuzzi, Sara Gimeno, Ana Martinez-Castillo, Ane Lete, Marta G. Delgado, Sandra Airoldi, Cristina Rodrigues Tavares, Marina Bláhová, Markéta Chytil, Petr Křen, Vladimír Abrescia, Nicola G. A. Ardá, Ana Bojarová, Pavla Jiménez-Barbero, Jesús Int J Mol Sci Article 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. MDPI 2021-06-01 /pmc/articles/PMC8199549/ /pubmed/34206141 http://dx.doi.org/10.3390/ijms22116000 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bertuzzi, Sara Gimeno, Ana Martinez-Castillo, Ane Lete, Marta G. Delgado, Sandra Airoldi, Cristina Rodrigues Tavares, Marina Bláhová, Markéta Chytil, Petr Křen, Vladimír Abrescia, Nicola G. A. Ardá, Ana Bojarová, Pavla Jiménez-Barbero, Jesús Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199549/ https://www.ncbi.nlm.nih.gov/pubmed/34206141 http://dx.doi.org/10.3390/ijms22116000 |
work_keys_str_mv | AT bertuzzisara crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT gimenoana crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT martinezcastilloane crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT letemartag crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT delgadosandra crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT airoldicristina crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT rodriguestavaresmarina crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT blahovamarketa crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT chytilpetr crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT krenvladimir crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT abrescianicolaga crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT ardaana crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT bojarovapavla crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers AT jimenezbarberojesus crosslinkingeffectsdictatethepreferenceofgalectinstobindlacnacdecoratedhpmacopolymers |