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

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 identi...

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Autores principales: Tseng, Kuei-Yao, Tzeng, Zheng-Hao, Cheng, Ting-Jen Rachel, Liang, Pi-Hui, Hung, Shang-Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326219/
https://www.ncbi.nlm.nih.gov/pubmed/35910734
http://dx.doi.org/10.3389/fchem.2022.947475
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author Tseng, Kuei-Yao
Tzeng, Zheng-Hao
Cheng, Ting-Jen Rachel
Liang, Pi-Hui
Hung, Shang-Cheng
author_facet Tseng, Kuei-Yao
Tzeng, Zheng-Hao
Cheng, Ting-Jen Rachel
Liang, Pi-Hui
Hung, Shang-Cheng
author_sort Tseng, Kuei-Yao
collection PubMed
description 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-GlcNS6OSO(2)NH(2)-IdoA2OS-OMe and IdoA2OS-GlcNS6NS-IdoA2OS-OMe, were rationally designed and synthesized as the Sulf-1 inhibitors with IC(50) values at 0.27 and 4.6 μM, respectively.
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spelling pubmed-93262192022-07-28 Design and Synthesis of 1-O- and 6′-C-Modified Heparan Sulfate Trisaccharides as Human Endo-6-O-Sulfatase 1 Inhibitors Tseng, Kuei-Yao Tzeng, Zheng-Hao Cheng, Ting-Jen Rachel Liang, Pi-Hui Hung, Shang-Cheng Front Chem Chemistry 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-GlcNS6OSO(2)NH(2)-IdoA2OS-OMe and IdoA2OS-GlcNS6NS-IdoA2OS-OMe, were rationally designed and synthesized as the Sulf-1 inhibitors with IC(50) values at 0.27 and 4.6 μM, respectively. Frontiers Media S.A. 2022-07-13 /pmc/articles/PMC9326219/ /pubmed/35910734 http://dx.doi.org/10.3389/fchem.2022.947475 Text en Copyright © 2022 Tseng, Tzeng, Cheng, Liang and Hung. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Tseng, Kuei-Yao
Tzeng, Zheng-Hao
Cheng, Ting-Jen Rachel
Liang, Pi-Hui
Hung, Shang-Cheng
Design and Synthesis of 1-O- and 6′-C-Modified Heparan Sulfate Trisaccharides as Human Endo-6-O-Sulfatase 1 Inhibitors
title Design and Synthesis of 1-O- and 6′-C-Modified Heparan Sulfate Trisaccharides as Human Endo-6-O-Sulfatase 1 Inhibitors
title_full Design and Synthesis of 1-O- and 6′-C-Modified Heparan Sulfate Trisaccharides as Human Endo-6-O-Sulfatase 1 Inhibitors
title_fullStr Design and Synthesis of 1-O- and 6′-C-Modified Heparan Sulfate Trisaccharides as Human Endo-6-O-Sulfatase 1 Inhibitors
title_full_unstemmed Design and Synthesis of 1-O- and 6′-C-Modified Heparan Sulfate Trisaccharides as Human Endo-6-O-Sulfatase 1 Inhibitors
title_short Design and Synthesis of 1-O- and 6′-C-Modified Heparan Sulfate Trisaccharides as Human Endo-6-O-Sulfatase 1 Inhibitors
title_sort design and synthesis of 1-o- and 6′-c-modified heparan sulfate trisaccharides as human endo-6-o-sulfatase 1 inhibitors
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326219/
https://www.ncbi.nlm.nih.gov/pubmed/35910734
http://dx.doi.org/10.3389/fchem.2022.947475
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