Design and Synthesis of 1-O- and 6'-C-Modified Heparan Sulfate Trisaccharides as Human Endo-6-O-Sulfatase 1 Inhibitors

Tseng, Kuei-YaoKuei-YaoTsengTzeng, Zheng-HaoZheng-HaoTzengCheng, Ting-Jen RachelTing-Jen RachelChengPI-HUI LIANGHung, Shang-ChengShang-ChengHung2024-03-252024-03-252022-07-132296-2646https://scholars.lib.ntu.edu.tw/handle/123456789/641335The extracellular human endo-6-O-sulfatases (Sulf-1 and Sulf-2) are responsible for the endolytic cleavage of the 6-sulfate groups from the internal D-glucosamine residues in the highly sulfated subdomains of heparan sulfate proteoglycans. A trisaccharide sulfate, IdoA2OS-GlcNS6S-IdoA2OS, was identified as the minimal size of substrate for Sulf-1. In order to study the complex structure with Sulf-1 for developing potential drugs, two trisaccharide analogs, IdoA2OS-GlcNS6OSO2NH2-IdoA2OS-OMe and IdoA2OS-GlcNS6NS-IdoA2OS-OMe, were rationally designed and synthesized as the Sulf-1 inhibitors with IC50 values at 0.27 and 4.6 μM, respectively.encarbohydrate chemistry; endo-6-O-sulfatases; glycosaminoglycans; heparan sulfate; inhibitorsDesign and Synthesis of 1-O- and 6'-C-Modified Heparan Sulfate Trisaccharides as Human Endo-6-O-Sulfatase 1 Inhibitorsjournal article10.3389/fchem.2022.947475359107342-s2.0-85134808775https://api.elsevier.com/content/abstract/scopus_id/85134808775