基于β-环糊精的多肽支臂星状聚合物的制备及性能

以β-环糊精(β-CD)为起始原料, 通过磺酰化及乙二胺基取代等过程, 制备具有端氨基的中间体β-环糊精(6-en-β-CD); 再以6-en-β-CD为引发剂, 通过赖氨酸N-羧基环内酸酐(Lys-NCA)和谷氨酸N-羧基环内酸酐(Glu-NCA)的混合开环聚合(ROP)和脱苄氧羰基(Cbz)保护等反应, 制备了以β-CD为核、 混聚多肽为支臂的星状聚合物6-聚(谷氨酸-赖氨酸)-β-CD]. 以基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)、 核磁共振波谱(NMR)和傅里叶变换红外光谱(FTIR)等对星状聚合物及中间体结构进行表征; 同时采用圆二色光谱(CD)和噻唑蓝(MTT)法对该聚合物的二级结构和体外毒性进行了考察. 结果表明, 所得星状聚合物的重均分子量(M_w)为4626, 多分散系数(PDI)为1.10, 平均聚合度(DP)为27.1; 在水溶液中星状聚合物的二级结构是无规则线团; 在5 mg/mL浓度下, 细胞存活率可达到94%以上, 没有呈现明显体外细胞毒性, 具有潜在的药用前景.

Preparation and Characterization of Star-shaped β-Cyclodextrin Based Polymer†

β-Cyclodextrin with terminal amino moiety(6-en-β-CD) was prepared by β-cyclodextrin(β-CD) as starting material through sulfonation and ethylenediamine substitution. Then, the target polymer6-poly(glumatic acid-lysine)-β-CD] was obtained by ring opening polymerization(ROP) of glumatic acid and lysine N-carboxyl anhydride(NCA) and deprotection of benzoxycarbonyl(Cbz), with β-CD and polypeptides as its core and branched arms, respectively. The characters of the star-shaped polymer and its corresponding intermediates were determined by matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS), nuclear magnetic resonance(NMR) and Fourier transform infrared spectroscopy(FTIR), respectively. Moreover, the secondary structure and the cytotoxicity in vitro were also detected by circular dichroism(CD) and methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay, respectively. The results showed that successful synthesis of the target polymer and its intermediates was achieved, and the molecular weight(M_w) of the target polymer, polydispersity index(PDI) and average degree of polymerization(DP) were 4626, 1.10 and 27.1, respectively. Furthermore, the secondary structure of the target polymer in water was random coil. The cell viability of human umbilical vein endothelial cells(HUVECs) could reach over 94% when the polymer concentration was up to 5 mg/mL, exhibiting no cell toxicity in vitro. In conclusion, our studies demonstrated that the polymer had potential applications in pharmacy industry.