Silk Sericin-inspired Poly-<italic style="font-style: italic">β</italic>-homoserine for Protein Protection

Jun-Yu Zhang; Jia-Yi Cai; Dong-Hui Zhang; Long-Qiang Liu; Zhong-Hua Zhi; Bing Li; Qi Chen; Run-Hui Liu

doi:10.1007/s10118-026-3691-9

Your Location：

Home >

Browse articles >

Silk Sericin-inspired Poly-β-homoserine for Protein Protection

RESEARCH ARTICLE | Updated：2026-08-31

- Silk Sericin-inspired Poly-β-homoserine for Protein Protection
- Chinese Journal of Polymer Science Vol. 44, Issue 9, Pages: 3066-3074(2026)
- Affiliations：
  
  a.State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China
  b.Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
  c.State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200438, China
- Author bio：
  
  rliu@ecust.edu.cn
- Funds：
- DOI：10.1007/s10118-026-3691-9
  CLC：
- Received：15 March 2026，
  
  Accepted：30 March 2026，
  
  Online First：10 July 2026，
  
  Published：05 September 2026
- Accepted：
Scan QR Code
Zhang, J. Y.; Cai, J. Y.; Zhang, D. H.; Liu, L. Q.; Zhi, Z. H.; Li, B.; Chen, Q.; Liu, R. H. Silk sericin-inspired poly-β-homoserine for protein protection. Chinese J. Polym. Sci. 2026, 44, 3066–3074

Jun-Yu Zhang, Jia-Yi Cai, Dong-Hui Zhang, et al. Silk Sericin-inspired Poly-β-homoserine for Protein Protection[J]. Chinese Journal of Polymer Science, 2026, 44(9): 3066-3074. DOI: 10.1007/s10118-026-3691-9.
Zhang, J. Y.; Cai, J. Y.; Zhang, D. H.; Liu, L. Q.; Zhi, Z. H.; Li, B.; Chen, Q.; Liu, R. H. Silk sericin-inspired poly-β-homoserine for protein protection. Chinese J. Polym. Sci. 2026, 44, 3066–3074 DOI： 10.1007/s10118-026-3691-9.

Jun-Yu Zhang, Jia-Yi Cai, Dong-Hui Zhang, et al. Silk Sericin-inspired Poly-β-homoserine for Protein Protection[J]. Chinese Journal of Polymer Science, 2026, 44(9): 3066-3074. DOI: 10.1007/s10118-026-3691-9. DOI：

摘要

Sericin exhibits a protein protective function and is characterized by a high serine content

which inspired us to explore the protein-stabilizing effects of poly-

-homoserine (

-HS).

-HS effectively stabilizes proteins with varying physicochemical properties under environmental stresses

such as elevated temperature and lyophilization

highlighting its significant potential for protein stabilization.

Abstract

Protein stability is a critical factor that limits its application in biopharmaceuticals

clinical diagnostics

and industrial production. The inherent instability of proteins renders them susceptible to loss of activity and function under external environmental stresses

thus necessitating the development of novel stabilizers to improve protein stability. Inspired by sericin

we developed heterochiral poly-

-homoserine (

-HS) that combines resistance to enzymatic degradation

straightforward synthesis

and precise composition control

while exhibiting favorable in vitro safety profile. The

-HS exhibits remarkable stabilizing effects on horseradish peroxidase (HRP) and

-galactosidase (

-Gal) when subjected to elevated temperature and lyophilization

respectively. Our research indicates that

-HS stabilizes proteins by assisting in the maintenance of their conformation and preventing aggregation. Additionally

-HS demonstrates stabilizing effects on proteins with diverse physicochemical properties. Therefore

this study suggests that the

-HS is a promising candidate for enhancing protein stability.

关键词

Keywords

references

Frokjaer, S.; Otzen, D. E. Protein drug stability: a formulation challenge. Nat. Rev. Drug Discovery 2005 , 4 , 298−306..

Hartl, F. U.; Bracher, A.; Hayer-Hartl, M. Molecular chaperones in protein folding and proteostasis. Nature 2011 , 475 , 324−332..

Wang, X.; Zhang, W. Chemical topology and complexity of protein architectures. Trends Biochem. Sci. 2018 , 43 , 806−817..

Ebrahimi, S. B.; Samanta, D. Engineering protein-based therapeutics through structural and chemical design. Nat. Commun. 2023 , 14 , 2411..

Leader, B.; Baca, Q. J.; Golan, D. E. Protein therapeutics: a summary and pharmacological classification. Nat. Rev. Drug Discovery 2008 , 7 , 21−39..

Zhang, S.; Gong, L.; Sun, Y.; Zhang, F.; Gao, W. An ultra-long-acting L-asparaginase synergizes with an immune checkpoint inhibitor in starvation-immunotherapy of metastatic solid tumors. Biomaterials 2025 , 312 , 122740..

Liu, H.; Zhao, X.; Chen, J.; Win, Y.; Cai, J. Unnatural foldamers as inhibitors of A β aggregation via stabilizing the A β helix. Chem. Commun. 2025 , 61 , 4586−4594..

Choi, J. M.; Han, S. S.; Kim, H. S. Industrial applications of enzyme biocatalysis: current status and fu ture aspects. Biotechnol. Adv. 2015 , 33 , 1443−1454..

O'Connell, A.; Barry, A.; Burke, A. J.; Hutton, A. E.; Bell, E. L.; Green, A. P.; O'Reilly, E. Biocatalysis: landmark discoveries and applications in chemical synthesis. Chem. Soc. Rev. 2024 , 53 , 2828−2850..

Rahban, M.; Ahmad, F.; Piatyszek, M. A.; Haertlé, T.; Saso, L.; Saboury, A. A. Stabilization challenges and aggregation in protein-based therapeutics in the pharmaceutical industry. RSC Advances 2023 , 13 , 35947−35963..

Rojekar, S.; Gholap, A. D.; Jadhav, K.; Shevalkar, G.; Sugandhi, V. V.; Pai, R. H.; Parikh, K.; Prajapati, M. K.; Desai, N.; Vora, L. K.; Ingle, R. G.; Paudel, K. R. Exploring protein aggregation in biological products: from mechanistic understanding to practical solutions. AAPS PharmSciTech 2025 , 26 , 189..

Chi, E. Y.; Krishnan, S.; Randolph, T. W.; Carpenter, J. F. Physical stability of proteins in aqueous solution: mechanism and driving forces in nonnative protein aggregation. Pharm. Res. 2003 , 20 , 1325−1336..

Kumru, O. S.; Joshi, S. B.; Smith, D. E.; Middaugh, C. R.; Prusik, T.; Volkin, D. B. Vaccine instability in the cold chain: mechanisms, analysis and formulation strategies. Biologicals 2014 , 42 , 237−259..

Butreddy, A.; Janga, K. Y.; Ajjarapu, S.; Sarabu, S.; Dudhipala, N. Instability of therapeutic proteins - an overview of stresses, stabilization mechanisms and analytical techniques involved in lyophilized proteins. Int. J. Biol. Macromol. 2021 , 167 , 309−325..

Sivasankaran, R. P.; Snell, K.; Kunkel, G.; Georgiou, P. G.; Puente, E. G.; Maynard, H. D. Polymer-mediated protein/peptide therapeutic stabilization: current progress and future directions. Prog. Polym. Sci. 2024 , 156 , 101867..

Fu, K.; Klibanov, A. M.; Langer, R. Protein stability in controlled-release systems. Nat. Biotechnol. 2000 , 18 , 24−25..

Shi, M.; McHugh, K. J. Strategies for overcoming protein and peptide instability in biodegradable drug delivery systems. Adv. Drug Delivery Rev. 2023 , 199 , 114904..

Ohtake, S.; Kita, Y.; Arakawa, T. Interactions of formulation excipients with proteins in solution and in the dried state. Adv. Drug Delivery Rev. 2011 , 63 , 1053−1073..

Kamerzell, T. J.; Esfandiary, R.; Joshi, S. B.; Middaugh, C. R.; Volkin, D. B. Protein-excipient interactions: mechanisms and biophysical characterization applied to protein formulation development. Adv. Drug Delivery Rev. 2011 , 63 , 1118−1159..

Arakawa, T.; Tsumoto, K.; Kita, Y.; Chang, B.; Ejima, D. Biotechnology applications of amino acids in protein purification and formulations. Amino Acids 2007 , 33 , 587−605..

Mao, T.; Xu, X.; Winkler, P. M.; Siri, C.; Poliukhina, E.; Silva, P. J.; Xu, N.; Hu, Y.; Al Zahabi, K.; La Polla, R.; Luo, Z.; Ong, Q.; Alexander-Katz, A.; Stellacci, F. Stabilizing effect of amino acids on protein and colloidal dispersions. Nature 2025 , 645 , 915−921..

Li, J.; Wang, H.; Wang, L.; Yu, D.; Zhang, X. Stabilization effects of saccharides in protein formulations: a review of sucrose, trehalose, cyclodextrins and dextrans. Eur. J. Pharm. Sci. 2024 , 192 , 106625..

Nicoud, L.; Cohrs, N.; Arosio, P.; Norrant, E.; Morbidelli, M. Effect of polyol sugars on the stabilization of monoclonal antibodies. Biophys. Chem. 2015 , 197 , 40−46..

Wang, W.; Wang, Y.; Wang, D. Dual effects of Tween 80 on protein stability. Int. J. Pharm. 2008 , 347 , 31−38..

Klich, J. H.; Kasse, C. M.; Mann, J. L.; Huang, Y.; d'Aquino, A. I.; Grosskopf, A. K.; Baillet, J.; Fuller, G. G.; Appel, E. A. Stable high-concentration monoclonal antibody formulations enabled by an amphiphilic copolymer excipient. Adv. Ther. 2023 , 6 , 2200102..

Li, B.; Wu, Y.; Zhang, W.; Zhang, S.; Shao, N.; Zhang, W.; Zhang, L.; Fei, J.; Dai, Y.; Liu, R. Efficient synthesis of amino acid polymers for protein stabilization. Biomater. Sci. 2019 , 7 , 3675−3682..

Chen, J.; Xiao, Y.; Lang, M. Temperature-sensitive micelles as artificial chaperones for insulin protection. Chinese J. Polym. Sci. 2025 , 43 , 350−359..

Zhang, C.; Lu, H. Helical nonfouling polypeptides for biomedical applications. Chinese J. Polym. Sci. 2022 , 40 , 433−446..

Hu, Y.; Li, C.; He, L.; Jin, C.; Liu, M. Mechanisms of chaperones as active assistant/Protector for proteins: insights from NMR studies. Chin. J. Chem. 2020 , 38 , 406−413..

Zhao, S.; Quan, S.; He, W.; Xu, L.; Hu, H.; Ma, Z.; Ma, R.; Huang, F.; Shi, L. Natural spy chaperone mimic: tailored nanochaperone with electrostatic-hydrophobic synergy to enhance protein folding regulation. J. Am. Chem. Soc. 2025 , 147 , 15357−15368..

Mutukuri, T. T.; Ling, J.; Du, Y.; Su, Y. C.; Zhou, Q. T. Effect of buffer salts on physical stability of lyophilized and spray-dried protein formulations containing bovine serum albumin and trehalose. Pharm. Res. 2023 , 40 , 1355−1371..

Kaushik, J. K.; Bhat, R. Why is trehalose an exceptional protein stabilizer An analysis of the thermal stability of proteins in the presence of the compatible osmolyte trehalose. J. Biol. Chem. 2003 , 278 , 26458−26465..

Panganiban, B.; Qiao, B.; Jiang, T.; DelRe, C.; Obadia, M. M.; Nguyen, T. D.; Smith, A. A. A.; Hall, A.; Sit, I.; Crosby, M. G.; Dennis, P. B.; Drockenmuller, E.; Olvera de la Cruz, M.; Xu, T. Random heteropolymers preserve protein function in foreign environments. Science 2018 , 359 , 1239−1243..

Rajan, R. S.; Li, T. S.; Aras, M.; Sloey, C.; Sutherland, W.; Arai, H.; Briddell, R.; Kinstler, O.; Lueras, A. M. K.; Zhang, Y.; Yeghnazar, H.; Treuheit, M.; Brems, D. N. Modulation of protein aggregation by polyethylene glycol conjugation: GCSF as a case study. Protein Sci. 2006 , 15 , 1063−1075..

Soutar, D. E.; Mack, H. F.; Ligorio, M.; Bissoyi, A.; Baker, A. N.; Gibson, M. I. PVAylation: precision end-functionalized poly(vinyl alcohol) for site-selective bioconjugation. Chem. Sci. 2025 , 16 , 9264−9275..

Charlton, L. M.; Barnes, C. O.; Li, C. G.; Orans, J.; Young, G. B.; Pielak, G. J. Residue-level interrogation of macromolecular crowding effects on protein stability. J. Am. Chem. Soc. 2008 , 130 , 6826−6830..

Lee, J.; Lin, E. W.; Lau, U. Y.; Hedrick, J. L.; Bat, E.; Maynard, H. D. Trehalose glycopolymers as excipients for pr otein stabilization. Biomacromolecules 2013 , 14 , 2561−2569..

Li, Z.; Zhu, K.; Ren, L.; Yuan, X. Sulfonium-containing glycopolypeptides tethering trehalose for protein stabilization. ACS Macro Lett. 2022 , 11 , 1278−1284..

Zhang, P.; Sun, F.; Tsao, C.; Liu, S.; Jain, P.; Sinclair, A.; Hung, H.; Bai, T.; Wu, K.; Jiang, S. Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity. Proc. Natl. Acad. Sci. U. S. A. 2015 , 112 , 12046−12051..

Zhang, J.; Xiao, X.; Zhang, D.; Liu, L.; Zhang, W.; Liang, Q.; Liu, R. The cheap silk sericin displaying chaperone-like activity to stabilize protein and facilitate protein refolding. CCS Chem. 2025 , 7 , 2185−2200..

Wang, J.; Liu, H.; Shi, X.; Qin, S.; Liu, J.; Lv, Q.; Liu, J.; Li, Q.; Wang, Z.; Wang, L. Development and application of an advanced biomedical material-silk sericin. Adv. Mater. 2024 , 36 , e2311593..

Kundu, S. C.; Dash, B. C.; Dash, R.; Kaplan, D. L. Natural protective glue pr otein, sericin bioengineered by silkworms: potential for biomedical and biotechnological applications. Prog. Polym. Sci. 2008 , 33 , 998−1012..

Yang, K.; Zhang, J.; Zhang, C.; Guan, J.; Ling, S.; Shao, Z. Hierarchical design of silkworm silk for functional composites. Chem. Soc. Rev. 2025 , 54 , 4973−5020..

Zhang, D.; Chen, Q.; Zhang, W.; Liu, H.; Wan, J.; Qian, Y.; Li, B.; Tang, S.; Liu, Y.; Chen, S.; Liu, R. Silk-inspired β -peptide materials resist fouling and the foreign-body response. Angew. Chem., Int. Ed. 2020 , 59 , 9586−9593..

Liu, R.; Chen, X.; Gellman, S. H.; Masters, K. S. Nylon-3 polymers that enable selective culture of endothelial cells. J Am Chem Soc 2013 , 135 , 16296−9..

Krainer, F. W.; Glieder, A. An updated view on horseradish peroxidases: recombinant production and biotechnological applications. Appl. Microbiol. Biotechnol. 2015 , 99 , 1611−1625..

Thakral, S.; Sonje, J.; Munjal, B.; Suryanarayanan, R. Stabilizers and their interaction with for mulation components in frozen and freeze-dried protein formulations. Adv. Drug Delivery Rev. 2021 , 173 , 1−19..

Juers, D. H.; Matthews, B. W.; Huber, R. E. LacZ β -galactosidase: structure and function of an enzyme of historical and molecular biological importance. Protein Sci . 2012 , 21 , 1792−1807..

Views

109

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Chemoselective Ring-opening Copolymerization of CO2-based Lactones towards Functional Polyesters

Development of Rapid Environment Degradable and Recyclable Poly(1,3-propylene glycol oxalate) via Ring-opening Polymerization of Seven-Membered Cyclic Oxalate

In situ Construction of Fluorinated Polyester-based Block Copolymer Electrolytes via Orthogonal Polymerization

Enhanced Segment Mobility Promotes Stereocomplex Crystallization in Polymer Blends via Elevated Segmental Miscibility

Tunable Circularly Polarized Luminescence of Helical Poly(phenylacetylene)s via Side-chain-to-Backbone Förster Resonance Energy Transfer

Related Author

Zhuo-Rui Zhang

Tian-Wen Bai

Sheng-Hao Li

Ting Shen

Jun-Jie Zeng

Kai-Hao Chen

Jun Ling

Xu-Feng Ni

Related Institution

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University

College of Biological, Chemical Sciences and Engineering, Jiaxing University

Key Laboratory of Medical Electronics and Digital Health of Zhejiang Province, Jiaxing University

Shandong Key Laboratory of High Performance Polyolefin Materials and Recycling; College of Polymer Science and Engineering, Qingdao University of Science and Technology

College of Chemistry, Chemical Engineering and Materials Science, Zaozhuang University

⁰

Silk Sericin-inspired Poly-β-homoserine for Protein Protection

DOI：10.1007/s10118-026-3691-9

摘要

Abstract

关键词

Keywords

references