Synthesis of bioactive (1→6)-β-glucose branched poly-amido-saccharides that stimulate and induce M1 polarization in macrophages
β-Glucans are of significant interest due to their potent antitumor and immunomodulatory activities. Nevertheless, the difficulty in purification, structural heterogenicity, and limited solubility impede the development of structure-property relationships and translation to therapeutic applications....
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10356/170856 |
| _version_ | 1826117775931736064 |
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| author | Xiao, Ruiqing Zeng, Jialiu Bressler, Eric M. Lu, Wei Grinstaff, Mark W. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Xiao, Ruiqing Zeng, Jialiu Bressler, Eric M. Lu, Wei Grinstaff, Mark W. |
| author_sort | Xiao, Ruiqing |
| collection | NTU |
| description | β-Glucans are of significant interest due to their potent antitumor and immunomodulatory activities. Nevertheless, the difficulty in purification, structural heterogenicity, and limited solubility impede the development of structure-property relationships and translation to therapeutic applications. Here, we report the synthesis of a new class of (1→6)-β-glucose-branched poly-amido-saccharides (PASs) as β-glucan mimetics by ring-opening polymerization of a gentiobiose-based disaccharide β-lactam and its copolymerization with a glucose-based β-lactam, followed by post-polymerization deprotection. The molecular weight (Mn) and frequency of branching (FB) of PASs is readily tuned by adjusting monomer-to-initiator ratio and mole fraction of gentiobiose-lactam in copolymerization. Branched PASs stimulate mouse macrophages, and enhance production of pro-inflammatory cytokines in a FB-, dose-, and Mn-dependent manner. The stimulation proceeds via the activation of NF-κB/AP-1 pathway in a Dectin-1-dependent manner, similar to natural β-glucans. The lead PAS significantly polarizes primary human macrophages towards M1 phenotype compared to other β-glucans such as lentinan, laminarin, and curdlan. |
| first_indexed | 2024-10-01T04:32:51Z |
| format | Journal Article |
| id | ntu-10356/170856 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:32:51Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1708562023-10-08T15:37:04Z Synthesis of bioactive (1→6)-β-glucose branched poly-amido-saccharides that stimulate and induce M1 polarization in macrophages Xiao, Ruiqing Zeng, Jialiu Bressler, Eric M. Lu, Wei Grinstaff, Mark W. Lee Kong Chian School of Medicine (LKCMedicine) Science::Biological sciences Beta-Glucans Immunoglobulin Enhancer β-Glucans are of significant interest due to their potent antitumor and immunomodulatory activities. Nevertheless, the difficulty in purification, structural heterogenicity, and limited solubility impede the development of structure-property relationships and translation to therapeutic applications. Here, we report the synthesis of a new class of (1→6)-β-glucose-branched poly-amido-saccharides (PASs) as β-glucan mimetics by ring-opening polymerization of a gentiobiose-based disaccharide β-lactam and its copolymerization with a glucose-based β-lactam, followed by post-polymerization deprotection. The molecular weight (Mn) and frequency of branching (FB) of PASs is readily tuned by adjusting monomer-to-initiator ratio and mole fraction of gentiobiose-lactam in copolymerization. Branched PASs stimulate mouse macrophages, and enhance production of pro-inflammatory cytokines in a FB-, dose-, and Mn-dependent manner. The stimulation proceeds via the activation of NF-κB/AP-1 pathway in a Dectin-1-dependent manner, similar to natural β-glucans. The lead PAS significantly polarizes primary human macrophages towards M1 phenotype compared to other β-glucans such as lentinan, laminarin, and curdlan. Published version This work was supported in part by Boston University and Boston University Nanotechnology Innovation Center (BUnano), and the National Institutes of Health (NIH R01EB017722 (M.W.G.), T32GM130546 (E.M.B.), and F30 CA257566 (E.M.B.)). 2023-10-08T08:24:37Z 2023-10-08T08:24:37Z 2022 Journal Article Xiao, R., Zeng, J., Bressler, E. M., Lu, W. & Grinstaff, M. W. (2022). Synthesis of bioactive (1→6)-β-glucose branched poly-amido-saccharides that stimulate and induce M1 polarization in macrophages. Nature Communications, 13(1), 4661-. https://dx.doi.org/10.1038/s41467-022-32346-5 2041-1723 https://hdl.handle.net/10356/170856 10.1038/s41467-022-32346-5 35945224 2-s2.0-85135733673 1 13 4661 en Nature Communications © 2022 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. application/pdf |
| spellingShingle | Science::Biological sciences Beta-Glucans Immunoglobulin Enhancer Xiao, Ruiqing Zeng, Jialiu Bressler, Eric M. Lu, Wei Grinstaff, Mark W. Synthesis of bioactive (1→6)-β-glucose branched poly-amido-saccharides that stimulate and induce M1 polarization in macrophages |
| title | Synthesis of bioactive (1→6)-β-glucose branched poly-amido-saccharides that stimulate and induce M1 polarization in macrophages |
| title_full | Synthesis of bioactive (1→6)-β-glucose branched poly-amido-saccharides that stimulate and induce M1 polarization in macrophages |
| title_fullStr | Synthesis of bioactive (1→6)-β-glucose branched poly-amido-saccharides that stimulate and induce M1 polarization in macrophages |
| title_full_unstemmed | Synthesis of bioactive (1→6)-β-glucose branched poly-amido-saccharides that stimulate and induce M1 polarization in macrophages |
| title_short | Synthesis of bioactive (1→6)-β-glucose branched poly-amido-saccharides that stimulate and induce M1 polarization in macrophages |
| title_sort | synthesis of bioactive 1 6 β glucose branched poly amido saccharides that stimulate and induce m1 polarization in macrophages |
| topic | Science::Biological sciences Beta-Glucans Immunoglobulin Enhancer |
| url | https://hdl.handle.net/10356/170856 |
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