基于β-环糊精的多肽支臂星状聚合物的制备及性能

doi:10.7503/cjcu20170561

高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (4): 793.doi: 10.7503/cjcu20170561

基于β-环糊精的多肽支臂星状聚合物的制备及性能

杨庆华¹(), 王龙刚², 柳杰¹, 陆勇³, 许华建¹, 陈天云³

1.合肥工业大学生物与医学工程学院, 合肥 230009
2. 燕山大学环境与化学工程学院, 秦皇岛 066004
3. 合肥工业大学化学化工学院, 合肥 230009

收稿日期:2017-08-17 出版日期:2018-04-10 发布日期:2018-03-18
作者简介:联系人简介: 杨庆华, 男, 博士, 讲师, 主要从事生物医用材料的制备和表征方面的研究. E-mail:yqhsina@126.com
基金资助:
中国博士后科学基金(批准号: 2015M571918)、合肥工业大学优秀青年人才培育B计划项目、中央高校基本科研业务费专项资金(批准号: JZ2014HGBZ0330)和合肥工业大学校级大学生创新训练计划项目(批准号: 2017CXCY490)资助

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

YANG Qinghua^1,^*(), WANG Longgang², LIU Jie¹, LU Yong³, CHEN Tianyun³

1. Department of Pharmacy, School of Biological and Medical Engineering,Hefei University of Technology, Hefei 230009, China
2. Department of Chemical Technology, School of Environmental and Chemical Engineering,Yanshan University, Qinghuangdao 066004, China
3. Department of Chemical Technology, School of Chemistry and Chemical Engineering,Hefei University of Technology, Hefei 230009, China

Received:2017-08-17 Online:2018-04-10 Published:2018-03-18
Contact: YANG Qinghua E-mail:yqhsina@126.com
Supported by:
† Supported by the China Postdoctoral Science Foundation Funded Project(No.2015M571918), the Fundamental Research Funds for the Central Universities, China(No.JZ2014HGBZ0330) and the Innovation Training Projects for Undergraduate Students of Hefei University of Technology, China(No.2017CXCY490)

摘要/Abstract

摘要：

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.

关键词: β-环糊精, 开环聚合, N-羧基环内酸酐, 星状聚合物, 生物相容性

Abstract:

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 polymer[6-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.

Key words: β-Cyclodextrin, Ring opening polymerization, N-Carboxyl anhydride, Star-shaped polymer, Biocompatibility

中图分类号:

O631.5

TrendMD:

杨庆华, 王龙刚, 柳杰, 陆勇, 许华建, 陈天云. 基于β-环糊精的多肽支臂星状聚合物的制备及性能. 高等学校化学学报, 2018, 39(4): 793.

YANG Qinghua, WANG Longgang, LIU Jie, LU Yong, CHEN Tianyun. Preparation and Characterization of Star-shaped β-Cyclodextrin Based Polymer^†. Chem. J. Chinese Universities, 2018, 39(4): 793.

图/表 12

Scheme 1 Synthesis route of 6-OTs-β-CD

Scheme 2 Synthesis route of 6-en-β-CD

Scheme 3 Synthesis route of Cbz-protected target polymer

Scheme 4 Synthesis route of the target polymer

Fig.1 FTIR spectra of 6-OTs-β-CD(a) and 6-en-β-CD(b)Inset: characteristic peaks of benzenoid ring in 6-OTs-β-CD.

Fig.2 MALDI-TOF-MS spectrum of the target polymer

Fig.3 1H NMR spectrum of the target polymer

Fig.4 Detailed scans of element nitrogen(N1s) of the target polymer

Fig.5 FTIR spectrum of the target polymer

Fig.6 CD spectroscopy of the target polypeptide in water

Fig.7 MTT assay results of the target polymer at different concentrations

Fig.8 Representative HUVECs pictures of 0.01 mg/mL(A) and 5 mg/mL(B) for the target polymer in MTT assay

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基于β-环糊精的多肽支臂星状聚合物的制备及性能

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

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基于β-环糊精的多肽支臂星状聚合物的制备及性能

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

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