Streamlined Synthesis and Immunomodulatory Effects of Ulvan Oligosaccharides from Marine Green Algae

Green algae, commonly used as a source of food nutrients, contain ulvan, which is a water-soluble sulfated heteropolysaccharide isolated from Ulva. Ulvan exhibits a range of biological properties, including antitumor, antiviral, anticoagulant, and immunomodulatory activities. Its sugar backbone consists of 1→4-linked disaccharide repeating units, which are categorized as ulvanobiuronic acids (types A_3'S and B_3'S) and ulvanobioses (types U_3'S and U_2S3'S). Despite its promising therapeutic potential, the detailed structure-activity relationship of ulvan remains unclear. In this study, an efficient strategy was developed, utilizing orthogonally protected α1→4-linked l-Rha-d-Glc, l-Rha-l-Ido, and l-Rha-d-Xyl derivatives as disaccharide building blocks to synthesize di-, tetra-, hexa-, and octasaccharides of types A_3'S, B_3'S, and U_3'S. The immunomodulatory effects of these compounds were evaluated through cytokine induction experiments. The results revealed that only the B_3'S and U_3'S octasaccharides had a significant influence on the gene expression of IL-1β, IL-6, IL-10, GM-CSF, and G-CSF. This chemical glycobiology approach offers valuable insights into the biomedical applications of marine ulvan oligosaccharides.