葡萄糖异构化对其糖聚合物蛋白识别功能的影响
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摘要
设计合成了具备良好的近红外吸收性能的苝酰亚胺大分子引发剂,并通过原子转移自由基聚合(ATRP)和后修饰方法制备了重复单元分别为一位羟基葡萄糖(1-Glc)和六位羟基葡萄糖(6-Glc)的糖聚合物.该聚合物在水溶液中能形成苝酰亚胺为核,糖聚合物为壳的纳米聚集体.通过动态光散射(DLS)、透射电子显微镜(TEM)和紫外-可见吸收光谱(UV-Vis)对聚合物在水溶液中的形貌、大小以及光学性能进行了分析表征,聚合物在650~750 nm有较好的近红外吸收特性;通过光声仪测试了聚合物的光声性能,结果表明苝酰亚胺糖聚合物具有较强的光声信号;为研究葡萄糖异构化对糖聚合物蛋白识别功能的影响,采用多种表征手段如浊度法、动态光散射研究了聚合物和凝集素半刀豆蛋白(concanavalin A,Con A)的结合.发现随着Con A凝集素的加入,PBI-1-Glc溶液的浊度和粒径有着明显的增加,而PBI-6-Glc则几乎没有变化;此外,还利用光声成像技术研究了糖聚合物与Con A之间的相互作用,Con A凝集素可使PBI-1-Glc聚合物的光声信号明显增加,此结果表明光声技术也可以有效地识别2种聚合物与凝集素之间的相互作用.实验结果显示,PBI-1-Glc聚合物与凝集素Con A有强的相互作用,而PBI-6-Glc聚合物则没有,这证实了单糖异构化在影响其与凝集素的特异性识别方面具有一定普适性.
Based on the biological properties of saccharides, saccharide-protein interaction, self-assembling ability and high quantum yield of perylene bisimide derivatives, glucose functionalized water-soluble perylene bisimide derivatives were designed. Tri-block glycopolymers with different sugar units, 1-linked glucose(1-Glc) and 6-linked glucose(6-Glc), were synthesized by atom transfer radical polymerization(ATRP) and click reaction, using perylene bisimide(PBI) as the initiator. Dynamic light scattering(DLS), transmission electron microscopy(TEM) and ultraviolet-visible absorption spectra(UV-Vis) were used to characterize the morphology, size and optical property of the glycopolymers in aqueous solution. The results show that the polymers had high absorption in the near IR region. In addition, the photoacoustic property of the polymers was studied by photoacoustic imaging. The results showed that the glycopolymers had strong photoacoustic signals. Moreover, a variety of characterizations including UV-Vis and DLS were conducted to observe the interaction between the two glycopolymers and Con A in order to study glyco-regioisomerism effect on lectin-binding. It was found that the turbidity and particle size of PBI-1-Glc solution increased significantly with the addition of Con A lectin, while PBI-6-Glc solution showed little change. Further more, photoacoustic imaging was also applied to study the recognition of glycopolymers and lectin. The results indicated that Con A could increase the photoacoustic signal of PBI-1-Glc solution, and photoacoustic technology could also be used to identify the interaction between two polymers and lectins effectively. In conclusion, the experimental results showed that PBI-1-Glc had a strong interaction with lectin Con A, whereas PBI-6-Glc did not, confirming that the monosaccharide isomerization effect on their biological function of glycopolymers had universality in a certain degree.
Based on the biological properties of saccharides, saccharide-protein interaction, self-assembling ability and high quantum yield of perylene bisimide derivatives, glucose functionalized water-soluble perylene bisimide derivatives were designed. Tri-block glycopolymers with different sugar units, 1-linked glucose(1-Glc) and 6-linked glucose(6-Glc), were synthesized by atom transfer radical polymerization(ATRP) and click reaction, using perylene bisimide(PBI) as the initiator. Dynamic light scattering(DLS), transmission electron microscopy(TEM) and ultraviolet-visible absorption spectra(UV-Vis) were used to characterize the morphology, size and optical property of the glycopolymers in aqueous solution. The results show that the polymers had high absorption in the near IR region. In addition, the photoacoustic property of the polymers was studied by photoacoustic imaging. The results showed that the glycopolymers had strong photoacoustic signals. Moreover, a variety of characterizations including UV-Vis and DLS were conducted to observe the interaction between the two glycopolymers and Con A in order to study glyco-regioisomerism effect on lectin-binding. It was found that the turbidity and particle size of PBI-1-Glc solution increased significantly with the addition of Con A lectin, while PBI-6-Glc solution showed little change. Further more, photoacoustic imaging was also applied to study the recognition of glycopolymers and lectin. The results indicated that Con A could increase the photoacoustic signal of PBI-1-Glc solution, and photoacoustic technology could also be used to identify the interaction between two polymers and lectins effectively. In conclusion, the experimental results showed that PBI-1-Glc had a strong interaction with lectin Con A, whereas PBI-6-Glc did not, confirming that the monosaccharide isomerization effect on their biological function of glycopolymers had universality in a certain degree.
引文
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2 Choi S K.Synthetic Multivalent Molecules:Concepts and Biomedical Applications.Hoboken:John Wiley&Sons,Inc,2004
3 Varki A.Glycobiology,1993,3:97-130
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5 Dam T K,Brewer C F.Chem Rev,2002,102:387-429
6 Lowary T L.J Am Chem Soc,2008,130:10031-10032
7 Walters D E.J Med Chem,2008,51:6235-6235
8 Balamurugan S S,Bantchev J B,Yang Y M,Mc Carley R L.Angew Chem,2005,117:4950-4954
9 Lin M C,Sun P F,Chen G S,Jiang M.Chem Commun,2014,50:9779-9782
10 Sun P F,Lin M C,Zhao Y,Chen G S,Jiang M.Colloids Surf B:Biointerfaces,2015,133:12-18
11 Lian X,Wu D,Song X,Zhao H.Macromolecules,2010,43(18):7434-7445
12 Su L,Zhao Y,Chen G,Jiang M.Polym Chem,2012,3(6):1560-1566
13 Dam T K,Brewer C F.Chem Rev,2002,102(2):387-430
14 Huang Yi(黄毅),Huang Jinhua(黄金花),Xie Qingji(谢青季),Yao Shouzhuo(姚守拙).Prog Chem(化学进展),2008,20:942-950
15 Park S,Shin I.Angew Chem Int Ed,2002,41:3180-3182
16 Wang D,Liu S,Trummer B J,Deng C,Wang A.Nat Biotechnol,2002,20:275-281
17 Park S,Lee M R,Pyo S J,Shin I.J Am Chem Soc,2004,126:4812-4819
18 Meng Jianqiang(孟建强),Dong Yongquan(董永全),Li Zichen(李子臣).Acta Polymerica Sinica(高分子学报),2010,(5):550-555
19 Munoz E M,Correa J,Riguera R,Fernandez-Megia E.J Am Chem Soc,2013,135:5966-5969
20 Xue C,Jog S P,Murthy P,Liu H.Biomacromolecules,2006,7:2470-2474
21 Olmsted I R,Kussrow A,Bornhop D J.Anal Chem,2012,84:10817-10822
22 Kelly T L,Lam M C W,Wolf M O.Bioconjugate Chem,2006,17:575-578
23 Wang Yijuan(汪一娟),Jiang Hongliang(蒋宏亮),Hu Yingqian(胡应乾),Zhu Kangjie(朱康杰).Acta Polymerica Sinica(高分子学报),2005,(4):524-528
24 Xue C,Jog S P,Murthy P,Liu H.Biomacromolecules,2006,7:2470-2474
25 Liu S,Bakovic L,Chen A.J Electroanal Chem,2006,591:210-216
26 Xiong Xiangyuan(熊向源),Li Zichen(李子臣),Du Fusheng(杜福胜),Li Fumian(李福绵).Acta Polymerica Sinica(高分子学报),2001,(6):787-792
27 Granville A M,Que’mener D,Davis T P,Barner-Kowollik C,Stenzel M H.Macromol Symp,2007,255:81-89
28 Sun P F,He Y,Lin M C,Yu Z,Ding Y,Chen G S,Jiang M.ACS Macro Lett,2014,3:96-101
29 BérubéM,Dowlut M,Hall D G.J Org Chem,2008,73:6471-6479
30 Yang J M,Favazza C,Chen R M,Yao J J,Cai X,Maslov K,Zhou Q F,Shuang K K,Wang L V.Nat Med,2012,18:1297-1302
31 Taruttis A,Van Dam G M,Ntziachristos V.Cancer Research,2015,75:1548-1559
32 Fan Q L,Cheng K,Yang Z,Zhang R P,Yang M,Hu X,Ma X W,Bu L H,Lu X M,Xiong X X,Huang W,Zhao H,Cheng Z.Adv mater,2015,27:843-847
33 Lu Xiaomei(卢晓梅),Chen Pengfei(陈鹏飞),Hu Wenbo(胡文博),Tang Yufu(唐玉富),Huang Wei(黄维),Fan Quli(范曲立).Prog Chem(化学进展),2017,29:119-126