Automated Assembly of Polyglucuronic Acids for Structural Explorations

Polyuronic acids are important biopolymers in marine organisms, where they contribute to extracellular matrix modulation, cell signaling, and carbon cycling. However, the intrinsic structural heterogeneity of polyuronic acids has hindered efforts to establish clear structure-function relationships. Here, we report an automated glycan assembly (AGA) approach that enables the precise synthesis of β-(1-4)-linked d-glucuronic acid (GlcA) oligomers with defined chain lengths and glycosidic linkage stereochemistry. Molecular dynamics simulations revealed a characteristic 2-fold helical conformation, with rigidity in short oligomers and enhanced flexibility emerging in longer sequences. The calcium binding behavior of these oligomers was explored by NMR titrations, revealing diffuse electrostatic binding rather than localized chelation. Polyglucuronic acid (PGA) oligomers are a well-defined molecular model for dissecting ion-mediated interactions and provide a framework for designing uronic acid-based glycomaterials with tunable properties.