Effects of Topological Poly(acrylic acid)s on Protein Conformation and Functions

An-qi Ye; Zhe-qi Li; Shi-chao You; Hao-lin Chen; Yi Shi; Li-xin Liu; Yong-ming Chen

doi:10.11777/j.issn1000-3304.2026.26137

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Effects of Topological Poly(acrylic acid)s on Protein Conformation and Functions

更新时间：2026-07-08

- Effects of Topological Poly(acrylic acid)s on Protein Conformation and Functions
- Acta Polymerica Sinica Pages: 1-19(2026)
- 作者机构：
  
  1.中山大学材料科学与工程学院聚合物复合材料及功能材料教育部重点实验室广州 510275
  2.河南大学化学与分子科学学院开封 475004
  3.河南大学抗病毒性传染病创新药物全国重点实验室郑州 450046
- 作者简介：
  
  Hao-lin Chen, E-mail: chenhlin58@mail.sysu.edu.cn
  Yong-ming Chen, E-mail: chenym35@mail.sysu.edu.cn
- 基金信息：
- DOI：10.11777/j.issn1000-3304.2026.26137
  CLC：
- CSTR：32057.14.GFZXB.2026.7646
- Received：24 April 2026，
  
  Accepted：26 May 2026，
  
  Online First：08 July 2026，
- 稿件说明：
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叶安淇, 黎哲祺, 游世超, 陈浩林, 石毅, 刘利新, 陈永明. 拓扑结构聚丙烯酸对蛋白构象及功能的影响. 高分子学报, doi: 10.11777/j.issn1000-3304.2026.26137.

Ye, A. Q.; Li, Z. Q.; You, S. C.; Chen, H. L.; Shi, Y.; Liu, L. X.; Chen, Y. M. Effects of topological poly(acrylic acid)s on protein conformation and functions. Acta Polymerica Sinica (in Chinese), doi: 10.11777/j.issn1000-3304.2026.26137.
叶安淇, 黎哲祺, 游世超, 陈浩林, 石毅, 刘利新, 陈永明. 拓扑结构聚丙烯酸对蛋白构象及功能的影响. 高分子学报, doi: 10.11777/j.issn1000-3304.2026.26137. DOI： CSTR： 32057.14.GFZXB.2026.7646.

Ye, A. Q.; Li, Z. Q.; You, S. C.; Chen, H. L.; Shi, Y.; Liu, L. X.; Chen, Y. M. Effects of topological poly(acrylic acid)s on protein conformation and functions. Acta Polymerica Sinica (in Chinese), doi: 10.11777/j.issn1000-3304.2026.26137. DOI： CSTR： 32057.14.GFZXB.2026.7646.

摘要

蛋白质二级结构与其生物功能密切相关，研究聚合物与蛋白相互作用及其调控规律具有重要意义. 线型聚丙烯酸(PAA)可通过与蛋白表面带正电氨基相互作用或诱导构象变化影响蛋白功能，但不同链拓扑结构PAA对蛋白构象及功能的影响尚缺乏系统研究. 本研究采用“相同拓扑结构下比较分子量、相近分子量下比较拓扑结构”的研究策略，通过可控聚合反应和点击化学，合成了一系列不同分子量的线型和分子刷型PAA，通过圆二色谱(CD)系统考察了聚合物分子量与拓扑结构对蛋白构象及功能的调控作用. 结果表明，对于低分子量蛋白，低分子量线型PAA可快速诱导蛋白二级结构由

-螺旋向

-折叠转变，且PAA分子量越高，构象转变达到平衡所需时间越长. 在相近分子量条件下，分子刷型PAA较线型PAA可加快低分子量蛋白构象由

-螺旋向

-折叠转变；而对于高分子量蛋白，线型PAA和刷型PAA影响也很大，但是与聚合物分子量和拓扑结构的关系不鲜明. 拓扑结构PAA对不同蛋白的功能影响不同. 对于

-半乳糖苷酶，刷型PAA可显著稳定其酶活性，而线型PAA则迅速破坏其酶活性. 对分子量相近但拓扑结构不同的线型与刷型PAA作为模型抗原卵清蛋白(OVA)的佐剂进行了小鼠免疫评价. 结果表明，线型PAA诱导的OVA特异性IgG滴度及脾细胞干扰素-

分泌水平均显著优于分子刷组. 结合体外构象动力学数据推断，刷型PAA引发的抗原二级结构快速剧烈重塑可能导致关键表位受损，而线型聚合物介导的温和渐进式构象调控更利于保护功能性表位的完整. 综上，聚合物分子量、拓扑结构是调控蛋白结构和功能的重要参数.

Abstract

Secondary structure of proteins greatly matters the functions

making the study of polymer-protein interactions and their regulatory mechanisms of great significance. Linear poly(acrylic acid) (PAA) affects protein function by interacting with positively charged amino groups on proteins or by

altering their secondary structure. However

the impact of other topological PAAs on protein conformation and functions remains unexplored. This study employed a research strategy of comparing molecular weights under the same topological structure and comparing topological structures under similar molecular weights. Through controlled polymerization and click chemistry

a series of linear and brush-type PAAs with different molecular weights were synthesized. Circular dichroism (CD) chromatography was used to investigate the regulatory effects of polymer molecular weight and topological structure on protein conformation and function. First

in the linear PAA system

it was found that low-molecular-weight linear PAAs could significantly convert low-molecular-weight proteins from

-helices to

-sheets in a short time; the higher the PAA molecular weight

the longer the incubation time required for the protein conformational transition to equilibrium. Comparing linear and brush-type PAAs with similar molecular weights

the brush-type PAA significantly accelerated the conformational transition of low-molecular-weight proteins from

-helices to

-sheets. For high-molecular-weight proteins

both topologic PAAs still changed protein conformation greatly

but no clear dependence on polymer molecular weight or topology was observed. Furthermore

we evaluated the functions of two proteins in the presence of topological PAAs. For

-galactosidase

molecular bottlebrush PAA stabilized enzyme activity

while linear PAA rapidly destroyed it. In mouse immunization with ovalbumin (OVA) as a model antigen

linear PAA induced significantly higher OVA-specific IgG titers and splenocyte IFN-

secretion than molecular bottlebrush PAA. Combining conformation change by CD

we speculated that the drastic remodeling by molecular bottlebrush PAA could damage critical epitopes of OVA

whereas the mild modulation by linear PAA preserved epit

ope integrity. In conclusion

polymer molecular weight and topology are important parameters for regulating protein structure and function.

关键词

Keywords

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