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
E-mail: chenhlin58@mail.sysu.edu.cn;
收稿:2026-04-24,
录用:2026-05-26,
网络首发:2026-07-28,
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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.
蛋白质二级结构与其生物功能密切相关,研究聚合物与蛋白质相互作用及调控规律具有重要意义. 线型聚丙烯酸(PAA)可结合蛋白表面氨基并诱导构象转变,但不同拓扑结构PAA对蛋白构象和功能的调控尚缺乏系统研究. 本文采用“相同拓扑对比分子量、相近分子量对比拓扑结构”的策略,合成系列线型与分子刷型PAA
利用圆二色谱探究聚合物结构对蛋白的调控规律. 结果表明,对于低分子量蛋白,线型PAA诱导蛋白由
α
-螺旋向
β
-折叠转变,分子量越高构象平衡耗时越长. 相近分子量下,分子刷型PAA可加快该构象转变. 高分子量蛋白构象变化与PAA结构关联性较弱. 拓扑结构PAA对不同蛋白的功能影响不同:分子刷型PAA稳定
β
-半乳糖苷酶活性,而线型PAA破坏酶活. 小鼠免疫实验证实,线型PAA作为卵清蛋白(OVA)佐剂可诱导更高水平特异性IgG与干扰素-
γ
. 机制上,分子刷引发抗原剧烈构象重塑易损伤表位,线型聚合物温和调控更利于保护功能性表位. 综上,聚合物分子量与拓扑结构是调控蛋白结构与功能的关键参数.
The secondary structure of proteins is tightly linked to their biological functions
and investigating polymer-protein interactions and their regulatory rules is of great significance. Linear poly(acrylic acid) (PAA) binds to amino groups on protein surfaces and triggers conformational transitions. However
systematic studies on how PAA with distinct topologies modulates protein conformation and function remain scarce. This work adopts the strategy of comparing molecular weights under identical to
pologies and contrasting topologies at comparable molecular weights. A series of linear and bottlebrush PAA samples are synthesized
and circular dichroism spectroscopy is employed to explore how polymer structures regulate proteins. The results reveal that linear PAA induces the transition from
α
-helix to
β
-sheet in low-molecular-weight proteins; longer equilibrium times for conformational conversion are observed at higher PAA molecular weights. At similar molecular weights
bottlebrush PAA accelerates this conformational transition. In contrast
the conformational changes of high-molecular-weight proteins show weak correlation with PAA structures. PAA topologies exert divergent effects on different proteins: bottlebrush PAA stabilizes
β
-galactosidase activity
whereas linear PAA impairs it. Mouse immunization assays verify that linear PAA acts as an adjuvant for ovalbumin (OVA) to elicit elevated levels of antigen-specific IgG and interferon-
γ
. Mechanistically
drastic antigen conformational remodeling induced by bottlebrush polymers tends to damage critical epitopes
while mild
gradual regulation by linear polymers better preserves functional epitopes. In summary
the molecular weight and topology of polymers serve as key parameters governing protein structure and function.
Arad E. ; Jelinek R. Catalytic amyloids . Trends Chem. , 2022 , 4 ( 10 ), 907 - 917 . doi: 10.1016/j.trechm.2022.07.001 http://dx.doi.org/10.1016/j.trechm.2022.07.001
Greenblatt J. F. ; Alberts B. M. ; Krogan N. J. Discovery and significance of protein-protein interactions in health and disease . Cell , 2024 , 187 ( 23 ), 6501 - 6517 . doi: 10.1016/j.cell.2024.10.038 http://dx.doi.org/10.1016/j.cell.2024.10.038
何苏宁 , 刘赛 , 张婷婷 , 史林启 , 马如江 . 基于动态共价键的纳米载体用于蛋白质药物递送的研究进展 . 高分子学报 , 2025 , 56 ( 8 ), 1293 - 1312 .
Le S. P. ; Krishna J. ; Gupta P. ; Dutta R. ; Li S. L. ; Chen J. H. ; Thayumanavan S. Polymers for disrupting protein-protein interactions: where are we and where should we be? Biomacromolecules , 2024 , 25 ( 10 ), 6229 - 6249 . doi: 10.1021/acs.biomac.4c00850 http://dx.doi.org/10.1021/acs.biomac.4c00850
孙颖 , 王伟杰 , 姚焰 , 刘青青 , 陈鱼 , 毛晓卉 , 朱丽萍 , 朱美芳 . 高分子材料在蛋白分离应用中的研究进展 . 高分子学报 , 2025 , 56 ( 8 ), 1313 - 1332 .
Romio M. ; Trachsel L. ; Morgese G. ; Ramakrishna S. N. ; Spencer N. D. ; Benetti E. M. Topological polymer chemistry enters materials science: expanding the applicability of cyclic polymers . ACS Macro Lett. , 2020 , 9 ( 7 ), 1024 - 1033 . doi: 10.1021/acsmacrolett.0c00358 http://dx.doi.org/10.1021/acsmacrolett.0c00358
Gomez D. C. ; Seth S. ; Mondal R. ; Koehler S. J. ; Baker J. G. ; Plate C. ; Anderson I. C. ; Smith M. R. ; Gloriod J. ; Gunter M. ; Welborn V. V. ; Deshmukh S. A. ; Figg C. A. Tuning polyacrylate composition to recognize and modulate fluorescent proteins . Angew. Chim. Int. Ed. , 2026 , 65 ( 2 ), e 20032 . doi: 10.1002/anie.202520032 http://dx.doi.org/10.1002/anie.202520032
Davis H. C. ; Posey N. D. ; Tew G. N. Protein binding and release by polymeric cell-penetrating peptide mimics . Biomacromolecules , 2022 , 23 ( 1 ), 57 - 66 . doi: 10.1021/acs.biomac.1c00929 http://dx.doi.org/10.1021/acs.biomac.1c00929
Karla S. ; Sorci M. ; Moussa B. ; Banik R. ; Petersen P. B. ; Plawsky J. ; Belfort G. Hydrogen bonds and electrostatics drive adhesion of polar proteins to hydrophilized polymer membranes . J. Colloid Interface Sci. , 2026 , 701 , 138530 . doi: 10.1016/j.jcis.2025.138530 http://dx.doi.org/10.1016/j.jcis.2025.138530
Karabasz A. ; Bzowska M. ; Szczepanowicz K. Biomedical applications of multifunctional polymeric nanocarriers: a review of current literature . Int. J. Nanomed. , 2020 , 15 , 8673 - 8696 . doi: 10.2147/ijn.s231477 http://dx.doi.org/10.2147/ijn.s231477
Ahmad Bhawani S. ; Husaini A. ; Ahmad F. B. ; Asaruddin M. R. Polymer based protein therapeutics . Curr. Protein Pept. Sci. , 2018 , 19 ( 10 ), 972 - 982 . doi: 10.2174/1389203718666170821162823 http://dx.doi.org/10.2174/1389203718666170821162823
朱真逸 , 宋万通 , 陈学思 . 高分子免疫佐剂材料 . 高分子学报 , 2023 , 54 ( 5 ), 534 - 549 .
Guo S. H. ; Fu D. W. ; Utupova A. ; Sun D. J. ; Zhou M. ; Jin Z. ; Zhao K. Applications of polymer-based nanoparticles in vaccine field . Nanotechnol. Rev. , 2019 , 8 ( 1 ), 143 - 155 . doi: 10.1515/ntrev-2019-0014 http://dx.doi.org/10.1515/ntrev-2019-0014
Porfiri M. C. ; Melnichuk N. ; Braia M. J. ; Brinatti C. ; Loh W. ; Romanini D. Analysis of the structure-function relationship of alpha amylase complexed with polyacrylic acid . Colloids Surf. B Biointerfaces , 2020 , 188 , 110787 . doi: 10.1016/j.colsurfb.2020.110787 http://dx.doi.org/10.1016/j.colsurfb.2020.110787
Pichon S. ; Bruyère I. ; Janicot S. ; Silhadi W. ; Pallardy S. ; Minutello A. M. ; Donazzolo Y. ; Latreille M. ; Beloeil L. ; Garcon N. ; Pagnon A. ; Jantet-Blaudez F. ; Piras-Douce F. Safety and immunogenicity of a cytomegalovirus (CMV) recombinant glycoprotein B (gB) vaccine in combination with polyacrylate or an emulsion-based adjuvants . Vaccine , 2026 , 80 , 128553 . doi: 10.1016/j.vaccine.2026.128553 http://dx.doi.org/10.1016/j.vaccine.2026.128553
Sahin Eguz I. ; Ihlamur M. ; Abamor E. S. ; Topuzogullari M. Synthesis and immunogenicity of the linear conjugates of polyacrylic acid and antigenic peptide of human papillomavirus . Eur. Polym. J. , 2022 , 176 , 111425 . doi: 10.1016/j.eurpolymj.2022.111425 http://dx.doi.org/10.1016/j.eurpolymj.2022.111425
Garinot M. ; Piras-Douce F. ; Probeck P. ; Chambon V. ; Varghese K. ; Liu Y. Q. ; Luna E. ; Drake D. ; Haensler J. A potent novel vaccine adjuvant based on straight polyacrylate . Int. J. Pharm. X , 2020 , 2 , 100054 . doi: 10.1016/j.ijpx.2020.100054 http://dx.doi.org/10.1016/j.ijpx.2020.100054
Sun H. ; Kabb C. P. ; Sims M. B. ; Sumerlin B. S. Architecture-transformable polymers: reshaping the future of stimuli-responsive polymers . Prog. Polym. Sci. , 2019 , 89 , 61 - 75 . doi: 10.1016/j.progpolymsci.2018.09.006 http://dx.doi.org/10.1016/j.progpolymsci.2018.09.006
Zhao W. C. ; Huo H. Y. ; Lu Z. Y. ; Sun Z. Y. Understanding local conformation in cyclic and linear polymers using molecular dynamics and point cloud neural network . Chinese J. Polym. Sci. , 2025 , 43 ( 5 ), 695 - 710 . doi: 10.1007/s10118-025-3293-y http://dx.doi.org/10.1007/s10118-025-3293-y
Shi Y. ; Hou W. M. ; Li Z. Q. ; Chen Y. M. Tailoring the architecture of molecular bottlebrushes via click grafting-onto strategy . Macromol. Rapid Commun. , 2023 , 44 ( 23 ), 2300362 . doi: 10.1002/marc.202300362 http://dx.doi.org/10.1002/marc.202300362
Zhang Z. ; Li Z. Q. ; Shi Y. ; Chen Y. M. Molecular bottlebrushes as emerging nanocarriers: material design and biomedical application . Langmuir , 2024 , 40 ( 14 ), 7286 - 7299 . doi: 10.1021/acs.langmuir.3c03701 http://dx.doi.org/10.1021/acs.langmuir.3c03701
Saha D. ; Witt C. L. ; Fatima R. ; Uchiyama T. ; Pande V. ; Song D. P. ; Fei H. F. ; Yavitt B. M. ; Watkins J. J. Opportunities in bottlebrush block copolymers for advanced materials . ACS Nano , 2025 , 19 ( 2 ), 1884 - 1910 . doi: 10.1021/acsnano.4c12021 http://dx.doi.org/10.1021/acsnano.4c12021
Arno M. C. ; Inam M. ; Coe Z. ; Cambridge G. ; MacDougall L. J. ; Keogh R. ; Dove A. P. ; O'Reilly R. K. Precision epitaxy for aqueous 1D and 2D poly(ε-caprolactone) assemblies. J. Am. Chem. Soc. , 2017 , 139 ( 46 ), 16980 - 16985 . doi: 10.1021/jacs.7b10199 http://dx.doi.org/10.1021/jacs.7b10199
Li H. A. ; Liu H. ; Nie T. Q. ; Chen Y. ; Wang Z. Y. ; Huang H. H. ; Liu L. X. ; Chen Y. M. Molecular bottlebrush as a unimolecular vehicle with tunable shape for photothermal cancer therapy . Biomaterials , 2018 , 178 , 620 - 629 . doi: 10.1016/j.biomaterials.2018.03.032 http://dx.doi.org/10.1016/j.biomaterials.2018.03.032
Xu L. ; Zhang Q. Y. ; Lu L. J. ; Shi Y. ; Liu L. X. ; Shen J. ; Chen Y. M. Unimolecular nano-contrast agent with ultrahigh relaxivity and very long retention for magnetic resonance lymphography . Nano Lett. , 2022 , 22 ( 10 ), 4090 - 4096 . doi: 10.1021/acs.nanolett.2c00796 http://dx.doi.org/10.1021/acs.nanolett.2c00796
Liu C. ; Luo J. H. Protein oligomer engineering: a new frontier for studying protein structure, function, and toxicity. Angew. Chim. Int. Ed ., 2023 , 62 ( 23 ), e 202216480 . doi: 10.1002/anie.202216480 http://dx.doi.org/10.1002/anie.202216480
Hoarau M. ; Badieyan S. ; Marsh E. N. G. Immobilized enzymes: understanding enzyme-surface interactions at the molecular level . Org. Biomol. Chem. , 2017 , 15 ( 45 ), 9539 - 9551 . doi: 10.1039/c7ob01880k http://dx.doi.org/10.1039/c7ob01880k
Sánchez-Morán H. ; Kaar J. L. ; Schwartz D. K. Supra-biological performance of immobilized enzymes enabled by chaperone-like specific non-covalent interactions . Nat. Commun. , 2024 , 15 ( 1 ), 2299 . doi: 10.1038/s41467-024-46719-5 http://dx.doi.org/10.1038/s41467-024-46719-5
Pavot V. ; Bisceglia H. ; Guillaume F. ; Montano S. ; Zhang L. N. ; Boudet F. ; Haensler J. A novel vaccine adjuvant based on straight polyacrylate potentiates vaccine-induced humoral and cellular immunity in cynomolgus macaques . Hum. Vaccines Immunother. , 2021 , 17 ( 7 ), 2336 - 2348 . doi: 10.1080/21645515.2020.1855956 http://dx.doi.org/10.1080/21645515.2020.1855956
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