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Sequence-defined antibody-recruiting macromolecules
Antibody-recruiting molecules represent a novel class of therapeutic agents that mediate the recruitment of endogenous antibodies to target cells, leading to their elimination by the immune system. Compared to single-ligand copies, macromolecular scaffolds presenting multiple copies of an antibody-b...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284026/ https://www.ncbi.nlm.nih.gov/pubmed/37350815 http://dx.doi.org/10.1039/d3sc01507f |
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author | Aksakal, Resat Tonneaux, Corentin Uvyn, Annemiek Fossépré, Mathieu Turgut, Hatice Badi, Nezha Surin, Mathieu De Geest, Bruno G. Du Prez, Filip. E. |
author_facet | Aksakal, Resat Tonneaux, Corentin Uvyn, Annemiek Fossépré, Mathieu Turgut, Hatice Badi, Nezha Surin, Mathieu De Geest, Bruno G. Du Prez, Filip. E. |
author_sort | Aksakal, Resat |
collection | PubMed |
description | Antibody-recruiting molecules represent a novel class of therapeutic agents that mediate the recruitment of endogenous antibodies to target cells, leading to their elimination by the immune system. Compared to single-ligand copies, macromolecular scaffolds presenting multiple copies of an antibody-binding ligand offer advantages in terms of increased complex avidity. In this study, we describe the synthesis of sequence-defined macromolecules designed for antibody recruitment, utilising dinitrophenol (DNP) as a model antibody-recruiting motif. The use of discrete macromolecules gives access to varying the spacing between DNP motifs while maintaining the same chain length. This characteristic enables the investigation of structure-dependent binding interactions with anti-DNP antibodies. Through solid-phase thiolactone chemistry, we synthesised a series of oligomers with precisely localised DNP motifs along the backbone and a terminal biotin motif for surface immobilisation. Utilising biolayer interferometry analysis, we observed that oligomers with adjacent DNP motifs exhibited enhanced avidity for anti-DNP antibodies. Molecular modelling provided insights into the structures and dynamics of the various macromolecules, shedding light on the accessibility of the ligands to the antibodies. Overall, our findings highlight that the use of sequence-defined macromolecules can contribute to our understanding of structure–activity relationships and provide insights for the design of novel antibody-recruiting therapeutic agents. |
format | Online Article Text |
id | pubmed-10284026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-102840262023-06-22 Sequence-defined antibody-recruiting macromolecules Aksakal, Resat Tonneaux, Corentin Uvyn, Annemiek Fossépré, Mathieu Turgut, Hatice Badi, Nezha Surin, Mathieu De Geest, Bruno G. Du Prez, Filip. E. Chem Sci Chemistry Antibody-recruiting molecules represent a novel class of therapeutic agents that mediate the recruitment of endogenous antibodies to target cells, leading to their elimination by the immune system. Compared to single-ligand copies, macromolecular scaffolds presenting multiple copies of an antibody-binding ligand offer advantages in terms of increased complex avidity. In this study, we describe the synthesis of sequence-defined macromolecules designed for antibody recruitment, utilising dinitrophenol (DNP) as a model antibody-recruiting motif. The use of discrete macromolecules gives access to varying the spacing between DNP motifs while maintaining the same chain length. This characteristic enables the investigation of structure-dependent binding interactions with anti-DNP antibodies. Through solid-phase thiolactone chemistry, we synthesised a series of oligomers with precisely localised DNP motifs along the backbone and a terminal biotin motif for surface immobilisation. Utilising biolayer interferometry analysis, we observed that oligomers with adjacent DNP motifs exhibited enhanced avidity for anti-DNP antibodies. Molecular modelling provided insights into the structures and dynamics of the various macromolecules, shedding light on the accessibility of the ligands to the antibodies. Overall, our findings highlight that the use of sequence-defined macromolecules can contribute to our understanding of structure–activity relationships and provide insights for the design of novel antibody-recruiting therapeutic agents. The Royal Society of Chemistry 2023-05-22 /pmc/articles/PMC10284026/ /pubmed/37350815 http://dx.doi.org/10.1039/d3sc01507f Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Aksakal, Resat Tonneaux, Corentin Uvyn, Annemiek Fossépré, Mathieu Turgut, Hatice Badi, Nezha Surin, Mathieu De Geest, Bruno G. Du Prez, Filip. E. Sequence-defined antibody-recruiting macromolecules |
title | Sequence-defined antibody-recruiting macromolecules |
title_full | Sequence-defined antibody-recruiting macromolecules |
title_fullStr | Sequence-defined antibody-recruiting macromolecules |
title_full_unstemmed | Sequence-defined antibody-recruiting macromolecules |
title_short | Sequence-defined antibody-recruiting macromolecules |
title_sort | sequence-defined antibody-recruiting macromolecules |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284026/ https://www.ncbi.nlm.nih.gov/pubmed/37350815 http://dx.doi.org/10.1039/d3sc01507f |
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