Structural analysis and accelerating wound healing function of a novel galactosylated glycosaminoglycan from the snail Helix lucorum

Diabetic foot ulcers (DFUs) as a nonhealing wound remain a clinical challenge, and the development of pro-healing and cost-effective drugs is in urgent need. Herein, we reported a novel galactosylated glycosaminoglycan (GAG) from the snail Helix lucorum, as an effective pro-healing compound. The snail GAG is composed of a heparan sulfate-like main chain and galactose side chains at C-3 of GlcNAc residue. Its main chain has a repeating disaccharide structure of → 4)-α-D-GlcNAc-(1 → 4)-α-L-IdoA_2S(1 →. This is the first example of glycosaminoglycan with galactose branches from mollusks. Pharmacological experiments showed that the H. lucorum GAG significantly promoted skin wound healing in both healthy and diabetic mice by accelerating granulation tissue regeneration, angiogenesis, and collagen deposition. The distinctive galactosylated substitution may play an important role on its pro-healing activity. Our discovery enriches the diversity of non-anticoagulant heparan sulfate-like glycosaminoglycans, and provides a potential candidate of pro-healing drug for treating diabetic wound.