AUTHOR=Tseng Kuei-Yao , Tzeng Zheng-Hao , Cheng Ting-Jen Rachel , Liang Pi-Hui , 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/journals/chemistry/articles/10.3389/fchem.2022.947475

DOI=10.3389/fchem.2022.947475

ISSN=2296-2646

ABSTRACT=<p>The extracellular human endo-6-<italic>O</italic>-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-GlcNS6OSO<sub>2</sub>NH<sub>2</sub>-IdoA2OS-OMe and IdoA2OS-GlcNS6NS-IdoA2OS-OMe, were rationally designed and synthesized as the Sulf-1 inhibitors with IC<sub>50</sub> values at 0.27 and 4.6 μM, respectively.</p>