A heparan-like glycosaminoglycan from the white jade snail: Precise structural elucidation, alkaline-induced artificial changes, and non-anticoagulant heparanase inhibition

White jade snail (a bred albino variant of Achatina fulica ) is widely used in China as an edible and medicinal resource. Previous studies have reported the overall structural characteristics of its glycosaminoglycan (GAG) at the polymer level; however, precise oligosaccharide evidence and structure-function relevance have remained insufficient. In this study, the heparan-like GAG from farmed white jade snails (AfH) was structurally elucidated using a bottom-up strategy based on well-defined oligosaccharides generated by β-eliminative and deaminative depolymerization, revealing a highly regular repeating unit -[4-D-GlcNAc-α1,4-L-IdoA 2S -α1,]-. Notably, alkaline processing was demonstrated to induce artificial structural alterations, including 2-O-desulfation of IdoA 2S , conversion of IdoA to GalA, and epimerization of GlcNAc to ManNAc. AfH exhibited potent heparanase inhibitory activity while showing negligible anticoagulant and P-selectin inhibition, with activity positively correlated with molecular weight and sulfate content. Structural variations showed distinct biological impacts, ManNAc introduction in a tetrasaccharide (Tetra-2) enhanced heparanase inhibition. Functionally, AfH significantly suppressed 4T1 cell migration and invasion and reduced pulmonary metastasis in mice. This work establishes AfH as a natural resource abundant, well-defined, non-anticoagulant heparan-like GAG with strong anti-metastatic potential, while highlighting alkaline processing as a critical determinant of GAG structural integrity and bioactivity.