Highly Efficient Chiral Separation Based on Alkali-proof Protein Immobilization by Covalent Organic Frameworks
Mingfang Yang
Key Laboratory of Biopharmaceutical Preparation and Delivery, State Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorYunlong Zheng
Key Laboratory of Biopharmaceutical Preparation and Delivery, State Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorYuqing Cai
College of Chemistry, Nankai University, Tianjin, 300071 China
Search for more papers by this authorJinbiao Guo
Key Laboratory of Biopharmaceutical Preparation and Delivery, State Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorAlong Zuo
Key Laboratory of Biopharmaceutical Preparation and Delivery, State Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorJiangyue Yu
Key Laboratory of Biopharmaceutical Preparation and Delivery, State Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorSainan Zhang
Functional Nanomaterials Laboratory, Centre for Micro/Nanomaterials and Technology, Key Laboratory of Photo-chemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorProf. Zhenjie Zhang
College of Chemistry, Nankai University, Tianjin, 300071 China
Search for more papers by this authorCorresponding Author
Prof. Yao Chen
Key Laboratory of Biopharmaceutical Preparation and Delivery, State Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences, Beijing, 100190 China
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300071 China
Haihe Laboratory of Synthetic Biology, 21 West 15th Avenue, Tianjin Airport Economic Area, Tianjin, 300308 China
Frontiers Science Center for Cell Responses, Nankai University, Tianjin, 300071 China
Search for more papers by this authorMingfang Yang
Key Laboratory of Biopharmaceutical Preparation and Delivery, State Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorYunlong Zheng
Key Laboratory of Biopharmaceutical Preparation and Delivery, State Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorYuqing Cai
College of Chemistry, Nankai University, Tianjin, 300071 China
Search for more papers by this authorJinbiao Guo
Key Laboratory of Biopharmaceutical Preparation and Delivery, State Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorAlong Zuo
Key Laboratory of Biopharmaceutical Preparation and Delivery, State Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorJiangyue Yu
Key Laboratory of Biopharmaceutical Preparation and Delivery, State Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorSainan Zhang
Functional Nanomaterials Laboratory, Centre for Micro/Nanomaterials and Technology, Key Laboratory of Photo-chemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorProf. Zhenjie Zhang
College of Chemistry, Nankai University, Tianjin, 300071 China
Search for more papers by this authorCorresponding Author
Prof. Yao Chen
Key Laboratory of Biopharmaceutical Preparation and Delivery, State Key Laboratory of Biochemical Engineering, Chinese Academy of Sciences, Beijing, 100190 China
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300071 China
Haihe Laboratory of Synthetic Biology, 21 West 15th Avenue, Tianjin Airport Economic Area, Tianjin, 300308 China
Frontiers Science Center for Cell Responses, Nankai University, Tianjin, 300071 China
Search for more papers by this authorAbstract
Chiral separation plays a pivotal role in both practical applications and industrial productions. However, traditional chiral stationary phases (CSPs) exhibit inherent instability in alkaline environments, presenting a significant challenge despite their importance. Herein, basophilic alcalase is creatively developed to fabricate ultrastable protein-based CSPs that can efficiently work under alkaline conditions. An in-depth theoretical simulation is conducted to unveil the unique three-dimensional conformation of alcalase, showing selective affinity towards various enantiomers of chiral amino acids and drugs, especially acidic substrates. Subsequently, an in situ assembly strategy is used to immobilize alcalase within a hydrazone-linked covalent organic framework (COF) platform. The generated protein-based CSPs enable successful baseline separation (Rs≥1.50) for various value-added compounds (e.g., non-steroidal drug, RS-flurbiprofen; nucleotide analog, RS-tenofovir) via high-performance liquid chromatography, surpassing the commercial chiral column. Furthermore, a systematic study reveals that increasing hydrophilicity and pore sizes of COFs can enhance the separation performance. Remarkably, the obtained CSPs demonstrated exceptional durability, maintaining performance for >2,400 runs. This study provides a new member to the protein library for CSPs, and represents an innovative and effective platform for CSPs with immense potential for the enantioseparation of acidic drugs.
Conflict of Interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
| Filename | Description |
|---|---|
| ange202420269-sup-0001-misc_information.pdf5.2 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1
- 1aM. M. M. Pinto, C. Fernandes, M. E. Tiritan, Molecules 2020, 25, 1931;
- 1bA. Higuchi, M. Tamai, Y. A. Ko, Y. I. Tagawa, Y. H. Wu, B. D. Freeman, J. T. Bing, Y. Chang, Q. D. Ling, Polym. Rev. 2010, 50, 113–143.
- 2S. Felletti, O. H. Ismail, C. De Luca, V. Costa, F. Gasparrini, L. Pasti, N. Marchetti, A. Cavazzini, M. Catani, Chromatographia 2019, 82, 65–75.
- 3
- 3aR. N. Patel, Coord. Chem. Rev. 2008, 252, 659–701;
- 3bE. Sanganyado, Z. Lu, Q. Fu, D. Schlenk, J. Gan, Water Res. 2017, 124, 527–542;
- 3cR. N. Patel, Biomol. Eng. 2013, 3, 741–777.
- 4
- 4aW. H. Brooks, W. C. Guida, K. G. Daniel, Curr. Top. Med. Chem. 2011, 11, 760–770;
- 4bM. Abram, M. Jakubiec, K. Kaminski, ChemMedChem 2019, 14, 1744–1761.
- 5A. Calcaterra, I. D'Acquarica, J. Pharm. Biomed. Anal. 2018, 147, 323–340.
- 6
- 6aC. Perrin, V. A. Vu, N. Matthijs, M. Maftouh, D. L. Massart, Y. Vander Heyden, J. Chromatogr. A 2002, 947, 69–83;
- 6bC. Perrin, N. Matthijs, D. Mangelings, C. Granier-Loyaux, M. Maftouh, D. L. Massart, Y. Vander Heyden, J. Chromatogr. A 2002, 966, 119–134;
- 6cD. Wistuba, V. Schurig, J. Chromatogr. A 2000, 875, 255–276.
- 7J. H. Zhang, S. M. Xie, L. M. Yuan, J. Sep. Sci. 2022, 45, 51–77.
- 8L. Fu, Z. G. Wang, E. C. Y. Yan, Int. J. Mol. Sci. 2011, 12, 9404–9425.
- 9P. Erlandsson, I. Marle, L. Hansson, R. Isaksson, G. Pettersson, C. Pettersson, J. Am. Chem. Soc. 1990, 112, 4573–4574.
- 10J. Haginaka, Chem. Pharm. Bull. 2022, 70, 458–468.
- 11
- 11aL. J. Xia, M. H. Tang, Z. D. Ding, L. Lin, H. F. Luo, R. He, Chin. J. Org. Chem. 2002, 22, 1018–1021;
- 11bH. Matsunaga, Q. Fu, J. Haginaka, Anal. Sci. 2002, 18, 27–30.
- 12W. Li, Y. Fan, C. Yan, Y. Du, T. Liang, C. Wang, L. Wang, L. Han, Q. Li, T. Liang, J. Mol. Liq. 2022, 367, 120300.
- 13F. Karush, J. Phys. Chem. 1952, 56, 70–77.
- 14B. Chankvetadze, TrAC Trends Anal. Chem. 2020, 122, 115709.
- 15
- 15aS. Zhang, Y. Zheng, H. An, B. Aguila, C.-X. Yang, Y. Dong, W. Xie, P. Cheng, Z. Zhang, Y. Chen, S. Ma, Angew. Chem. Int. Ed. 2018, 57, 16754–16759;
- 15bY. Feng, H. Wang, S. Zhang, Y. Zhao, J. Gao, Y. Zheng, P. Zhao, Z. Zhang, M. J. Zaworotko, P. Cheng, S. Ma, Y. Chen, Adv. Mater. 2019, 31, 1805148;
- 15cY. Feng, R. Shi, M. Yang, Y. Zheng, Z. Zhang, Y. Chen, Angew. Chem. Int. Ed. 2023, 62, e202302436.
- 16
- 16aS. Y. Ding, W. Wang, Chem. Soc. Rev. 2013, 42, 548–568;
- 16bH. Furukawa, O. M. Yaghi, J. Am. Chem. Soc. 2009, 131, 8875–8883;
- 16cK. Y. Geng, T. He, R. Y. Liu, S. Dalapati, K. T. Tan, Z. P. Li, S. S. Tao, Y. F. Gong, Q. H. Jiang, D. L. Jiang, Chem. Rev. 2020, 120, 8814–8933.
- 17
- 17aY. M. Feng, Y. Xu, S. C. Liu, D. Wu, Z. Q. Su, G. Chen, J. H. Liu, G. L. Li, Coord. Chem. Rev. 2022, 459, 214414;
- 17bC. E. Wang, K. M. Liao, ACS Appl. Mater. Interfaces 2021, 13, 56752–56776;
- 17cC. Sicard, Angew. Chem. Int. Ed. 2023, 62, e202213405.
- 18Z. Palmai, D. Perahia, C. Lionne, J. Fidy, E. Balog, L. Chaloin, Arch. Biochem. Biophys. 2011, 511, 88–100.
- 19M. H. Hyun, S. C. Han, J. S. Jin, W. Lee, Chromatographia 2000, 52, 473–476.
- 20M. E. Marrazzo, J. P. Foley, Chromatographia 2023, 86, 743–750.
- 21J. Haginaka, Y. Miyano, Y. Saizen, C. Seyama, T. Murashima, J. Chromatogr. A 1995, 708, 161–168.
- 22M. A. Mazorra-Manzano, J. C. Ramirez-Suarez, R. Y. Yada, Crit. Rev. Food Sci. Nutr. 2018, 58, 2147–2163.
- 23K. Pourmohammadi, E. Abedi, Food Sci. Nutr. 2021, 9, 3988–4006.
- 24
- 24aM. J. Abraham, T. Murtola, R. Schulz, S. Páll, J. C. Smith, B. Hess, E. Lindahl, SoftwareX 2015, 1–2, 19–25;
10.1016/j.softx.2015.06.001 Google Scholar
- 24bQ.-K. Zhang, X.-Q. Zhang, J. Wan, N. Yao, T.-L. Song, J. Xie, L.-P. Hou, M.-Y. Zhou, X. Chen, B.-Q. Li, R. Wen, H.-J. Peng, Q. Zhang, J.-Q. Huang, Nat. Energy 2023, 8, 725–735;
- 24cV. Ponnuchamy, Chem. Phys. Lett. 2020, 754, 137707;
- 24dJ. Zhang, T. Lu, Phys. Chem. Chem. Phys. 2021, 23, 20323–20328;
- 24eT. Lu, F. Chen, J. Comput. Chem. 2012, 33, 580–592;
- 24fT. Lu, Sobtop, Version 1.0 (dev3.1), http://sobereva.com/soft/Sobtop (accessed on 01/03/20323).
- 25H. Sun, Y. Li, S. Tian, L. Xu, T. Hou, Phys. Chem. Chem. Phys. 2014, 16, 16719–16729.
- 26Y. L. Zheng, S. N. Zhang, J. B. Guo, R. X. Shi, J. Y. Yu, K. P. Li, N. Li, Z. J. Zhang, Y. Chen, Angew. Chem. Int. Ed. 2022, 61, e202208744.
- 27M. G. Zuza, N. Z. Milasinovic, M. M. Jonovic, J. R. Jovanovic, M. T. K. Krusic, B. M. Bugarski, Z. D. Knezevic-Jugovic, Bioprocess Biosyst. Eng. 2017, 40, 1713–1723.
- 28P. W. Tardioli, J. Pedroche, R. L. C. Giordano, R. Fernández-Lafuente, J. M. Guisán, Biotechnol. Progr. 2003, 19, 352–360.
- 29D. C. Carter, J. X. Ho, Adv. Protein Chem. 1994, 45, 153–203.
- 30X. Fan, L. Cao, L. Geng, Y. Ma, Y. Wei, Y. Wang, Int. J. Biol. Macromol. 2021, 186, 616–638.
- 31A. Strandberg, A. Nyström, S. Behr, A. Karlsson, Chromatographia 1999, 50, 215–222.
- 32K. K. Unger, R. Skudas, M. M. Schulte, J. Chromatogr. A 2008, 1184, 393–415.
- 33Z. Wang, S. Zhang, Y. Chen, Z. Zhang, S. Ma, Chem. Soc. Rev. 2020, 49, 708–735.
- 34H. Ma, S. Wang, Y. Ren, X. Liang, Y. Wang, Z. Zhu, G. He, Z. Jiang, Chem. Res. Chin. Univ. 2022, 38, 325–338.
This is the
German version
of Angewandte Chemie.
Note for articles published since 1962:
Do not cite this version alone.
Take me to the International Edition version with citable page numbers, DOI, and citation export.
We apologize for the inconvenience.
