@ARTICLE{10.3389/fchem.2022.947475, AUTHOR={Tseng, Kuei-Yao and Tzeng, Zheng-Hao and Cheng, Ting-Jen Rachel and Liang, Pi-Hui and Hung, Shang-Cheng}, TITLE={Design and Synthesis of 1-O- and 6′-C-Modified Heparan Sulfate Trisaccharides as Human Endo-6-O-Sulfatase 1 Inhibitors}, JOURNAL={Frontiers in Chemistry}, VOLUME={10}, YEAR={2022}, URL={https://www.frontiersin.org/articles/10.3389/fchem.2022.947475}, DOI={10.3389/fchem.2022.947475}, ISSN={2296-2646}, ABSTRACT={The 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.} }