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Progress in Chemistry 2024, Vol. 36 Issue (3): 416-429 DOI: 10.7536/PC230706 Previous Articles   Next Articles

• Review •

Functionalization and Application of Polymer-Modified Proteins

Jiang Wan, Jingze Zhang, Hongling Chen, Hanmei Shen, Zhen Wang, Chun Zhang()   

  1. College of life science and technology, Huazhong University of Science and Technology, Wuhan 430000, China
  • Received: Revised: Online: Published:
  • Contact: * e-mail: chunzhang@hust.edu.cn
  • Supported by:
    National Natural Science Foundation of China(22275062); National Natural Science Foundation of China(22005110); Undergraduates Research Training Program(S202310487273)
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As a kind of important biological macromolecules, proteins have been widely used in chemical and medical fields, such as biocatalysis, drug delivery, and molecular imaging due to their special three-dimensional spatial structure and high catalytic activity. However, there are a series of problems in the practical application of proteins. For example, proteins are easily inactivated in extreme environments. Protein drugs have strong immunogenicity in vivo, which leads to short half-life of drugs and causes adverse reactions in patients easily. Their low solubility in organic solvents limits their use in organic solvents. In order to solve the above problems, researchers have developed methods such as protein engineering and co-immobilization, but there are corresponding shortcomings. Polymer modification is one of the important methods, which can improve the properties of proteins from many aspects and expand the application of proteins. From this point of view, this review focuses on the latest research and classical literature on polymer-modified proteins, and introduces their ingenious modification methods to synthesize materials with excellent properties. The principle, practical application, existing problems and solutions of improving protein stability and activity, immunogenicity, solubility and self-assembly by polymer modification are summarized. On this basis, the challenges and possible development trends in the commercial and clinical translation of this strategy are analyzed.

Contents

1 Introduction

2 Stability and activity

2.1 Stability to temperature and pH

2.2 Stability to protease hydrolysis

2.3 Stability of chemical denaturants

2.4 Enhanced enzyme activity

2.5 Regulation of enzyme activity

3 Immunogenicity

4 Solubility

5 Self-assembly

5.1 Drug delivery

5.2 Molecular imaging

6 Conclusion and outlook

Fig. 1 The principles and advantages and disadvantages of different grafting methods.
Fig. 2 Polymer modifications enhance protein stability by stabilizing the structure of the protein’s partially unfolded intermediate[1]
Fig. 3 PAA forms a cross-linked network structure around catalase to restrict the proximity of macromolecules such as protease and increase the resistance to protease hydrolysis[53]
Fig. 4 The synthesis principle of GOX/HRP-PHPMA conjugates and the process of realizing complex enzyme cascade reaction to increase reaction efficiency[62]
Fig. 5 Synthesis of the thermally responsive polymer-protein conjugate system. Then the conjugate capture IS. Finally, the captured IS is recovered by thermal precipitation[92]
Fig. 6 Synthesis of doxorubicin-loaded BSA-PCL vesicles with surface-modified ligands and its increased targeting to tumor tissue [99]
Fig. 7 Synthesis, pH response and tumor specific imaging of HSA-PDPA/ICG (HDI) nanoprobes[30]
Fig. 8 Measures to avoid decreased activity of protein- polymer conjugates: A reversible linkage; B site-specific modifications; C gene editing
Table 1 Examples of current alternatives to PEG in use and development. PG, poly (glycerol); PAOx, poly (2-oxazoline)s
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