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Investigating the stabilisation of IFN-α2a by replica exchange molecular dynamics simulation

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Abstract

Current biopharmaceutical drugs are mainly a class of peptides or proteins that play an essential role in the treatment of many diseases. Such peptides/proteins are usually thermally unstable and may lose their bioactivity when exposed to ambient conditions. Therefore, they are not suitable for long-term storage. Lyophilisation is the most common method to prolong shelf life of solid peptide/protein drugs; however, the freeze-drying process can lead to irreversible damage. In the present study, human interferon-alpha 2a (IFN-α2a) was selected as a model protein drug; four disaccharides (β-lactose, β-maltose, sucrose, and trehalose) were selected as bioactive protectants. We investigated the effects of different protectants on IFN-α2a under various ambient conditions (vacuum, dry state, and aqueous solution) using replica exchange molecular dynamics simulation. The protective effect of β-maltose on IFN-α2a was the highest in aqueous solution and dry state, β-lactose showed a poor protective effect in all three conditions, the performance of sucrose was good in all conditions, and trehalose showed a better protective effect under vacuum conditions and in aqueous solution. Disaccharides form H-bonds with water, thereby preventing water from the tertiary structure of proteins. Trehalose forms strong H-bonds with water which explains its extraordinary stability.

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Funding

This work was supported by the National Natural Science Foundation of China (Contract No. 61832019, 61503244), the Key Research Area Grant 2016YFA0501703 of the Ministry of Science and Technology of China, SJTU JiRLMDS Joint Research Fund, and the Science and Technology Commission of Shanghai Municipality (Grant: 19430750600). The work also was supported by Open Funding Project of State Key Laboratory of Microbial Metabolism (MMLKF21-11).

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Authors and Affiliations

  1. Institute of Biothermal Science and Technology, University of Shanghai for Science and Technology, Shanghai, 20093, China

    Daixi Li, Peiqin Chen, Qingli Dong & Baolin Liu

  2. Physics and Chemistry Department, Milwaukee School of Engineering, Milwaukee, WI, 53202, USA

    Wujie Zhang

  3. State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center On Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, China

    Dong-qing Wei

  4. Peng Cheng Laboratory, Shenzhen, 518055, China

    Dong-qing Wei

  5. Injection Laboratory, Shanghai Tofflon Science and Technology Co, Ltd, Shanghai, 201108, China

    Baisong Guo

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  1. Daixi Li
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Contributions

Daixi Li supervised research, Peiqin Chen performed the analysis and wrote the manuscript, and Daixi Li and Baolin Liu performed the molecular dynamics simulation. Wujie Zhang and Dong-qing Wei contributed significantly to analysis and manuscript preparation, and Qingli Dong and Baisong Guo helped perform the analysis with constructive discussions.

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Correspondence to Daixi Li.

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Li, D., Chen, P., Dong, Q. et al. Investigating the stabilisation of IFN-α2a by replica exchange molecular dynamics simulation. J Mol Model 28, 232 (2022). https://doi.org/10.1007/s00894-022-05212-w

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  • DOI: https://doi.org/10.1007/s00894-022-05212-w

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