Synthesis of bioactive (1→6)-β-glucose branched poly-amido-saccharides that stimulate and induce M1 polarization in macrophages
Year: 2022
Type: article
Abstract: 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.
Source: Nature Communications
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $5,890
OpenAlex ID: W4291020924