- Author
- Resat Aksakal (UGent) , Corentin Tonneaux, Annemiek Uvyn (UGent) , Mathieu Fossépré, Hatice Turgut (UGent) , Nezha Badi (UGent) , Mathieu Surin, Bruno De Geest (UGent) and Filip Du Prez (UGent)
- Organization
- Project
- Abstract
- 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.
- Keywords
- BINDING, MOLECULES
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HAAESXRE1FV1P7N13Z6V7S85
- MLA
- Aksakal, Resat, et al. “Sequence-Defined Antibody-Recruiting Macromolecules.” CHEMICAL SCIENCE, vol. 14, no. 24, 2023, pp. 6572–78, doi:10.1039/d3sc01507f.
- APA
- Aksakal, R., Tonneaux, C., Uvyn, A., Fossépré, M., Turgut, H., Badi, N., … Du Prez, F. (2023). Sequence-defined antibody-recruiting macromolecules. CHEMICAL SCIENCE, 14(24), 6572–6578. https://doi.org/10.1039/d3sc01507f
- Chicago author-date
- Aksakal, Resat, Corentin Tonneaux, Annemiek Uvyn, Mathieu Fossépré, Hatice Turgut, Nezha Badi, Mathieu Surin, Bruno De Geest, and Filip Du Prez. 2023. “Sequence-Defined Antibody-Recruiting Macromolecules.” CHEMICAL SCIENCE 14 (24): 6572–78. https://doi.org/10.1039/d3sc01507f.
- Chicago author-date (all authors)
- Aksakal, Resat, Corentin Tonneaux, Annemiek Uvyn, Mathieu Fossépré, Hatice Turgut, Nezha Badi, Mathieu Surin, Bruno De Geest, and Filip Du Prez. 2023. “Sequence-Defined Antibody-Recruiting Macromolecules.” CHEMICAL SCIENCE 14 (24): 6572–6578. doi:10.1039/d3sc01507f.
- Vancouver
- 1.Aksakal R, Tonneaux C, Uvyn A, Fossépré M, Turgut H, Badi N, et al. Sequence-defined antibody-recruiting macromolecules. CHEMICAL SCIENCE. 2023;14(24):6572–8.
- IEEE
- [1]R. Aksakal et al., “Sequence-defined antibody-recruiting macromolecules,” CHEMICAL SCIENCE, vol. 14, no. 24, pp. 6572–6578, 2023.
@article{01HAAESXRE1FV1P7N13Z6V7S85,
abstract = {{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.}},
author = {{Aksakal, Resat and Tonneaux, Corentin and Uvyn, Annemiek and Fossépré, Mathieu and Turgut, Hatice and Badi, Nezha and Surin, Mathieu and De Geest, Bruno and Du Prez, Filip}},
issn = {{2041-6520}},
journal = {{CHEMICAL SCIENCE}},
keywords = {{BINDING,MOLECULES}},
language = {{eng}},
number = {{24}},
pages = {{6572--6578}},
title = {{Sequence-defined antibody-recruiting macromolecules}},
url = {{http://doi.org/10.1039/d3sc01507f}},
volume = {{14}},
year = {{2023}},
}
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