绿藻鼠李聚糖模拟物的制备与抗EV71病毒活性评价  

Efficient synthesis and anti-EV71 activity study of green alga rhamnan glycomimetics

作　　者：李昕茹 孙继芹 仇会鑫 任莉 张萍[1] 王伟[1,2] 于广利 蔡超[1,2] LI Xin-ru;SUN Ji-qin;QIU Hui-xin;REN Li;ZHANG Ping;WANG Wei;YU Guang-li;CAI Chao(Key Laboratory of Marine Drugs,Ministry of Education,Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China;Laboratory for Marine Drags and Bioproducts of Qingdao Pilot National Laboratory for Marine Science and Technology,Qingdao 266237,China;CP Pharmaceutical Qingdao Co.,Ltd.,Qingdao 266555,China)

机构地区：[1]中国海洋大学海洋药物教育部重点实验室,山东省糖科学与糖工程重点实验室,医药学院,山东青岛266003 [2]青岛海洋科学与技术试点国家实验室海洋药物与生物制品功能实验室,山东青岛266237 [3]正大制药(青岛)有限公司,山东青岛266555

出　　处：《中国海洋药物》2022年第3期1-9,共9页Chinese Journal of Marine Drugs

基　　金：国家重大新药创制项目(2018ZX09735004);国家自然科学基金重大项目(81991522)资助。

摘　　要：目的 海洋绿藻中含有丰富的硫酸化鼠李聚糖,具有抗病毒、抗肿瘤等多样生物活性。然而由于天然提取的鼠李聚糖结构复杂,限制了其构效关系的深入研究,设计开发结构均一、质量可控的天然鼠李聚糖模拟物,对于推动其作为药物开发具有重要意义。方法 以α-L-鼠李单糖为起始原料,通过衍生修饰和烯烃复分解开环聚合(ROMP)反应,首先制备了线性鼠李糖聚合物;然后以聚酰胺胺(PAMAM)为骨架,基于“先臂后核”的设计思路,制备树枝状-星型鼠李糖聚合物。对制备的鼠李糖聚合物进行硫酸化修饰,模拟天然硫酸化绿藻多糖,并对其抗病毒活性开展研究。结果 通过烯烃复分解开环聚合反应成功制备了线性鼠李糖聚合物,并开发了1种以树枝状大分子PAMAM为骨架制备星型鼠李糖聚合物的高效方法。结论 通过单体聚合和末端枝接聚合法成功制备线性及树枝状-星型的天然绿藻鼠李聚糖模拟物,并证明该系列模拟物具有抗EV71病毒活性。Objective Marine green alga contains abundant sulfated rhamnose plysaccharides, which possesses various biological activities including antiviral and antitumor, etc. However, due to the complexity of the structure of natural rhamnose polysaccharide, few studies reported its structure-activity relationship. How to design and develop natural rhamnose mimics with uniform structure and controllable quality was of great significance to promote its drug development. Methods By using rhamnose monosaccharide as starting material, linear rhamnose-based polymer was synthesized by derivatization and ring-opening metathesis polymerization(ROMP). Meanwhile, a series of dendrimer-star rhamnose polymers were prepared based on the idea of “arm first” with polyamide amine(PAMAM) as skeleton. The rhamnose polymers were sulfated to simulate the natural sulfated polysaccharides from green alga, and their antiviral activities were studied. Results Based on the ROMP polymerization of linear rhamnose polymers, the efficient end grafting polymerization of PAMAM was developed for the synthesis of dendrimer-star rhamnose-based polymers.Conclusion In this study, the linear and dendrimer-star like rhamnan mimetics of green alga were successfully prepared by monomer polymerization and end grafting polymerization, which was proved to possess antiEV71 virus activities.

关 键 词：鼠李糖 聚酰胺胺 树枝状-星型糖聚合物 烯烃复分解开环聚合反应 抗病毒活性 

分 类 号：R914[医药卫生—药物化学]