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 (M_n) 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 M_n-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.

β-葡聚糖因其有效的抗肿瘤和免疫调节活性而备受关注。然而，纯化困难、结构异质性和有限的溶解度阻碍了结构-性质关系的发展和转化为治疗应用。在这里，我们报道了通过基于龙胆二糖的二糖β-内酰胺的开环聚合合成了一类新的（1→6）-β-葡萄糖支链聚酰胺糖（PAS）作为β-葡聚糖模拟物，并且它与葡萄糖基β-内酰胺共聚，然后进行聚合后脱保护。通过调节共聚过程中单体与引发剂的比例和龙胆二糖-内酰胺的摩尔分数，可以轻松调节 PAS 的分子量 ( M _n ) 和支化频率 (FB)。分支 PAS 刺激小鼠巨噬细胞，并以 FB、剂量和M _n依赖性方式增强促炎细胞因子的产生。刺激通过以 Dectin-1 依赖性方式激活 NF-κB/AP-1 通路来进行，类似于天然 β-葡聚糖。与其他 β-葡聚糖（如香菇多糖、昆布多糖和凝乳多糖）相比，先导 PAS 显着将人类原代巨噬细胞极化为 M1 表型。