文献类型：期刊文献

英文题名：Microwave-assisted synthesis of highly sulfated mannuronate glycans as potential inhibitors against SARS-CoV-2

作者：Zhu, Yirong[1];Wang, Xiaotong[1];Lu, Siqian[1];Zheng, Jibin[1];Liang, Youling[1];Zhang, Liangliang[1];Fang, Pengfei[2];Xu, Peng[2];Yu, Biao[2];Yang, You[1]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm,Shanghai Key Lab New Drug Design,Minist, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Shanghai Inst Organ Chem, Chinese Acad Sci, State Key Lab Chem Biol, 345 Lingling Rd, Shanghai 200032, Peoples R China

年份：2024

卷号：22

期号：19

起止页码：3986

外文期刊名：ORGANIC & BIOMOLECULAR CHEMISTRY

收录：;EI(收录号：20241916068277);WOS:【SCI-EXPANDED(收录号:WOS:001216695400001)】；

基金：Financial support from the National Natural Science Foundation of China (22071054 and 21871081), the Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission), the Taishan Industrial Experts Program (tscx202312168), and the Opening Project of Shanghai Key Laboratory of New Drug Design (21DZ2271600) is gratefully acknowledged.

语种：英文

外文关键词：Carboxylation - Diseases - Negative ions - Polysaccharides - Sulfur compounds

摘要：Algae-based marine carbohydrate drugs are typically decorated with negative ion groups such as carboxylate and sulfate groups. However, the precise synthesis of highly sulfated alginates is challenging, thus impeding their structure-activity relationship studies. Herein we achieve a microwave-assisted synthesis of a range of highly sulfated mannuronate glycans with up to 17 sulfation sites by overcoming the incomplete sulfation due to the electrostatic repulsion of crowded polyanionic groups. Although the partially sulfated tetrasaccharide had the highest affinity for the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, the fully sulfated octasaccharide showed the most potent interference with the binding of the RBD to angiotensin-converting enzyme 2 (ACE2) and Vero E6 cells, indicating that the sulfated oligosaccharides might inhibit the RBD binding to ACE2 in a length-dependent manner. Sulfated mannuronate glycans with up to 17 sulfation sites were synthesized using a microwave-assisted approach and evaluated as inhibitors against SARS-CoV-2.