A structurally defined galactoglucan from Arisaema erubescens with a multi-target tumor-associated protein binding domain.

As targeted therapy assumes an increasingly pivotal role in comprehensive cancer treatment, there is a growing imperative to develop natural drugs that exhibit low toxicity and minimal side effects. Polysaccharides derived from the traditional Chinese herbal medicine Arisaema erubescens have been reported to show antitumor potential, however the key structural features and specific molecular targets responsible for their pharmacological effects are still vague. To address this question, a homogeneous polysaccharide TNX05 (Mw ≈ 9 kDa) was obtained and characterized from Arisaema erubescens. Structural analysis suggested that TNX05 was a galactoglucan with a backbone of 1, 4-α-D-Glcp, 1, 4-β-D-Glcp, and 1, 3-β-D-Galp residues, with side chains-→1-α/β-D-Glcp-(6 → 1)-α-D-Glcp and →1)-α-D-Glcp-substituted at the C-4 and C-6 of the 1, 4-α-D-Glcp units, respectively. Combining enzymatic hydrolysis, molecular docking, and protein-binding assays we showed a key core domain (TNX05II), which exhibited micromolar-range binding affinity for ten tumor-associated targets: Glypican-6 (GPC-6), glucuronic acid epimerase (Glce), S100 calcium-binding protein A4 (S100A4), S100A6, nucleoside diphosphate kinase 1 (NME1), fibroblast growth factor 17 (FGF17), proto-oncogene tyrosine-protein kinase Src (SRC), kelch-like ECH-associated protein 1 (KEAP1), Galectin-3 (Gal-3), and protein phosphatase 3 catalytic subunit alpha (PPP3CA). Additionally, TNX05II was significantly resistant to α-glucosidase degradation. This study suggests a possible key structure-target relationship underlying TNX05's antitumor activity, providing a molecular basis for the antitumor mechanism of Arisaema polysaccharides.