Functional structural domain synthesis of anti-pancreatic carcinoma pectin-like polysaccharide RN1
文献类型：期刊论文
| 作者 | Cai, Deqin1,2; He, Fei1,2; Wu, Shengjie1,2; Wang, Zixuan1,2; Bian, Ya1,2; Wen, Chang1,2; Ding, Kan1,2,3,4
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| 刊名 | CARBOHYDRATE POLYMERS
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| 出版日期 | 2024-03-01 |
| 卷号 | 327页码:11 |
| 关键词 | Polysaccharide Pectin Functional structural domain Pancreatic cancer Glycan synthesis RN1 |
| ISSN号 | 0144-8617 |
| DOI | 10.1016/j.carbpol.2023.121668 |
| 通讯作者 | Ding, Kan(dingkan@simm.ac.cn) |
| 英文摘要 | The great structural and functional diversity supports polysaccharides as favorable candidates for new drug development. Previously we reported that a drug candidate pectin-like natural polysaccharide, RN1 might target galectin-3 (Gal-3) to impede pancreatic cancer cell growth in vivo. However, the quality control of polysaccharide-based drug research faces great challenges due to the heterogeneity. A potential solution is to synthesize structurally identified subfragments of this polysaccharide as alternatives. In this work, we took RN1 as an example, and synthesized five subfragments derived from the putative repeating units of RN1. Among them, pentasaccharide 4 showed an approximative binding affinity to Gal-3 in vitro, as well as an antiproliferative activity against pancreatic BxPC-3 cells comparable to that of RN1. Further, we scaled up pentasaccharide 4 to gram-scale in an efficient synthetic route with a 6.9 % yield from D-galactose. Importantly, pentasaccharide 4 significantly suppressed the growth of pancreatic tumor in vivo. Based on the mechanism complementarity of galactin-3 inhibitor and docetaxel, the combination administration of pentasaccharide 4 and docetaxel afforded better result. The result suggested pentasaccharide 4 was one of the functional structural domains of polysaccharide RN1 and might be a leading compound for anti-pancreatic cancer new drug development. |
| WOS关键词 | GALECTIN-3 ; CANCER ; ANGIOGENESIS ; GEMCITABINE ; DOCETAXEL ; HEPARIN ; CELL |
| 资助项目 | National Key Research and Devel- opment Program of China[2022YFA1303802] ; Shanghai Municipal Science and Technology Major Project ; National Natural Science Foundation of China[32271332] ; National Natural Science Foundation of China[31870801] ; Yangfan Project of Shanghai Science and Technology Commission[20YF1457300] ; High-level New R D Institute[2019B090904008] ; Department of Science and Technology of Guangdong Province[2021B0909050003] ; Zhongshan Science and Technology Bureau ; Zhongshan Municipal Bureau of Science and Technology |
| WOS研究方向 | Chemistry ; Polymer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001136395300001 |
| 出版者 | ELSEVIER SCI LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/308529]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Ding, Kan |
| 作者单位 | 1.Univ Chinese Acad Sci, Sch Med, 19A Yuquan Rd, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Drug Res Ctr, Glycochemistry & Glycobiol Lab, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Glycochemistry & Glycobiol Lab, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cai, Deqin,He, Fei,Wu, Shengjie,et al. Functional structural domain synthesis of anti-pancreatic carcinoma pectin-like polysaccharide RN1[J]. CARBOHYDRATE POLYMERS,2024,327:11. |
| APA | Cai, Deqin.,He, Fei.,Wu, Shengjie.,Wang, Zixuan.,Bian, Ya.,...&Ding, Kan.(2024).Functional structural domain synthesis of anti-pancreatic carcinoma pectin-like polysaccharide RN1.CARBOHYDRATE POLYMERS,327,11. |
| MLA | Cai, Deqin,et al."Functional structural domain synthesis of anti-pancreatic carcinoma pectin-like polysaccharide RN1".CARBOHYDRATE POLYMERS 327(2024):11. |
入库方式： OAI收割
来源：上海药物研究所
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