biostudies-literatureHe PNHLBI NIH HHS7438https://www.ebi.ac.uk/biostudies/studies/S-EPMC9718760biostudies-literatureUnknown13(1)Complex carbohydrates (glycans) are major players in all organisms due to their structural, energy, and communication roles. This last essential role involves interacting and/or signaling through a plethora of glycan-binding proteins. The design and synthesis of glycans as potential drug candidates that selectively alter or perturb metabolic processes is challenging. Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. An artificial sugar donor with a sulfhydryl functionality is synthesized and enzymatically incorporated into polysaccharide chains utilizing heparosan synthase. Used alone, this donor adds a single thio-sugar onto thNature communicationsChemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors.PMC9718760R01 HL144970Zhang FLinhardt RJXia KPham TLiu JZhang XAlmond AGreen DEBaytas SDeAngelis PLHe PXu YfalseChemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors.Complex carbohydrates (glycans) are major players in all organisms due to their structural, energy, and communication roles. This last essential role involves interacting and/or signaling through a plethora of glycan-binding proteins. The design and synthesis of glycans as potential drug candidates that selectively alter or perturb metabolic processes is challenging. Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. An artificial sugar donor with a sulfhydryl functionality is synthesized and enzymatically incorporated into polysaccharide chains utilizing heparosan synthase. Used alone, this donor adds a single thio-sugar onto th2022-01-01T00:00:00Z2022 Dec2025-04-19T22:59:59.916Z2025-04-19T22:59:59.916ZS-EPMC97187603646067010.1038/s41467-022-34788-3