化学学报 ›› 2015, Vol. 73 ›› Issue (8): 815-818.DOI: 10.6023/A15040267 上一篇    下一篇

研究论文

基于G-四联体的聚多肽-DNA水凝胶响应性研究

邵昱a, 李闯a, 周旭a, 陈平b, 杨忠强a, 李志波b, 刘冬生a   

  1. a 有机光电子与分子工程教育部重点实验室 清华大学化学系 北京 100084;
    b 中国科学院化学研究所 北京 100190
  • 收稿日期:2015-04-19 出版日期:2015-08-14 发布日期:2015-06-02
  • 通讯作者: 刘冬生 E-mail:liudongsheng@tsinghua.edu.cn
  • 基金资助:

    项目受国家重点基础研究发展计划(973 program, No. 2013CB932803)和国家自然科学基金(Nos. 91027046, 21121004)资助.

Responsive Polypeptide-DNA Hydrogel Crosslinked by G-quadruplex

Shao Yua, Li Chuanga, Zhou Xua, Chen Pingb, Yang Zhongqianga, Li Zhibob, Liu Dongshenga   

  1. a Key Laboratory of Organic Optoelectronics & Molecular Engineering of the Ministry of Education, Department of Chemistry, Tsinghua University, Beijing 100084;
    b Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190
  • Received:2015-04-19 Online:2015-08-14 Published:2015-06-02
  • Supported by:

    Project supported by the National Basic Research Program of China (973 program, No. 2013CB932803) and the National Natural Science Foundation of China (Nos. 91027046 & 21121004).

利用铜催化的点击反应合成了侧链接枝DNA的聚多肽, 基于DNA自组装的理念, 将含有两段鸟嘌呤(G)的序列引入到体系中, 结合G-四联体在钾离子存在的情况下能够形成分子间四链结构的特性, 获得了具有热响应和离子响应性的聚多肽-DNA超分子水凝胶. 此凝胶制备过程具有原位、快速等特点, 构筑基元具有可设计的响应性和良好的生物相容性. 综合以上特点, 此超分子水凝胶在组织工程和三维生物打印等领域具有潜在的应用.

关键词: DNA, 聚多肽, 自组装, G-四联体, 水凝胶, 响应性

In the past thirty years, DNA molecule has received considerable attention as a promising building material due to its precise base-paring recognition, the programmable sequences, the predictable secondary structures, etc. Based on DNA self-assembly technique, DNA supramolecular hydrogels can be fabricated which are crosslinked networks swollen in an aqueous phase by the supramolecular interaction and also have widely applications in the biomedical field. In this paper, a new type of DNA-based supramolecular hydrogel was prepared by simply mixing two components: Polypeptide-DNA and G-quadruplex. We have successfully synthesized single-stranded DNA (ssDNA) grafted polypeptide via the copper-catalyzed click reaction. By introducing the intermolecular G-quadruplex structure, which is rich in guanine and is capable of forming a four-stranded structure in the presence of potassium, the hydrogel can be formed by DNA hybridization in a fast and in-situ manner and also obtain thermal and ionic responsive gel-sol transition, respectively. In this experiment, we firstly used polyacrylamide gel electrophoresis (PAGE), circular dichroism spectra (CD), UV-Vis spectroscopy to demonstrate the G-quadruplex structure formation, and the assembling process was efficient which are formed the parallel structure and the melting temperature (Tm) was about 43 ℃. Then by the rheological tests, the shear-storage modulus (G') was obviously higher (up to 2.4 kPa) than the shear-loss modulus (G") over the entire time range, and a minimum concentration of 0.5 wt% polypeptide-DNA was required to form a gel-like state, and the mechanical strength of the DNA hydrogels increased with increasing concentration of the DNA building blocks. What’s more, the hydrogels can switch between the gel and the sol state when changing the temperature from 25 to 50 ℃ many times, indicating that the DNA hydrogels respond to thermal in a reversible way. At last, by using the properties of crown ether complexing potassium ion, the DNA hydrogel can obtain the ion responsiveness properties. Due to its designable responsiveness and good biocompatibility, this supramolecular hydrogel would have great potential applications in tissue engineering and 3D bioprinting field.

Key words: DNA, polypeptide, self-assembly, G-quadruplex, hydrogel, responsiveness