Fluorescent discrimination for snake venom via a dual-mode supramolecular sensor array
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Han-Wen Tian
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Dong-Sheng Guo
Abstract
Precise snake venom identification is the prerequisite for clinical treatment, production of antiserum, basic research, and other applications. Unfortunately, it is still a challenging task which mainly originates from their extraordinary complicated protein composition. Differential sensing strategy was applied benefiting from its advantage in discrimination of complex mixtures. Herein, A dual-mode supramolecular fluorescent sensor array based on the heteromultivalent sensing strategy was developed. The heteromultivalent macrocyclic coassemblies with strong and pan-selective binding to proteins were employed to construct sensor units. Fluorescence intensity and anisotropy signals were integrated, which were expected to show multidimensional information of proteins, such as surface groups, protein structures, and molecular weights. Finally, a supramolecular sensor array with the ability of facile, rapid and general species-specific identification and taxonomic classification for snake venom was constructed. The sensor array also demonstrated its advantage in semiquantitative analysis and multi-level identification, suggesting its great potential for practical use.
Funding source: Fundamental Research Funds for the Central Universities
Funding source: National Natural Science Foundation of China
Award Identifier / Grant number: 22101142
Acknowledgments
Financial supported by NSFC (22101142) and the Fundamental Research Funds for the Central Universities, which are gratefully acknowledged. The authors also thank Prof. Bart Jan Ravoo at Westfälische Wilhelms-Universität Münster for supplying the amphiphilic cyclodextrin used in this work.
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Research ethics: Not applicable.
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Informed consent: Not applicable.
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Author contributions: H. Tian and J.Tian conducted the experimental procedures, analyzed the data, and wrote the initial draft. X. Hu and D. Guo were responsible for the topic design and article revision. All authors have accepted responsibility for the entire content of this manuscript and approved its submission. The author has accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The author states no conflict of interest.
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Research funding: Financial supported by NSFC (22101142) and the Fundamental Research Funds for the Central Universities.
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Data availability: Not applicable.
References
1. Oliveira, A. L.; Viegas, M. F.; da Silva, S. L.; Soares, A. M.; Ramos, M. J.; Fernandes, P. A. The Chemistry of Snake Venom and its Medicinal Potential. Nat. Rev. Chem. 2022, 6, 451–69; https://doi.org/10.1038/s41570-022-00393-7.Suche in Google Scholar PubMed PubMed Central
2. Stocklin, R.; Mebs, D.; Boulain, J. C.; Panchaud, P. A.; Virelizier, H.; Gillard-Factor, C. Methods Mol. Biol. 2000, 146, 317–35.Suche in Google Scholar
3. Ferraz, C. R.; Arrahman, A.; Xie, C.; Casewell, N. R.; Lewis, R. J.; Kool, J.; Cardoso, F. C. Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis. Front. Ecol. Evol. 2019, 7, 218; https://doi.org/10.3389/fevo.2019.00218.Suche in Google Scholar
4. Tu, A. T. Adv. Exp. Med. Biol. 1996, 391, 37–62.10.1007/978-1-4613-0361-9_3Suche in Google Scholar PubMed
5. Knudsen, C.; Jurgensen, J. A.; Fons, S.; Haack, A. M.; Friis, R. U. W.; Dam, S. H.; Bush, S. P.; White, J.; Laustsen, A. H. Snakebite Envenoming Diagnosis and Diagnostics. Front. Immunol. 2021, 12, 661457; https://doi.org/10.3389/fimmu.2021.661457.Suche in Google Scholar PubMed PubMed Central
6. Long, C.; Wu, F.; Lu, Q.; Xie, B.; Shen, C.; Li, J.; Deng, Y.; Liang, P.; Yu, Y.; Lai, R. A Strategy for Efficient Preparation of Genus-Specific Diagnostic Antibodies for Snakebites. Front. Immunol. 2021, 12, 775678; https://doi.org/10.3389/fimmu.2021.775678.Suche in Google Scholar PubMed PubMed Central
7. Zheng, Z.; Geng, W.-C.; Gao, J.; Mu, Y.-J.; Guo, D.-S. Differential Calixarene Receptors Create Patterns that Discriminate Glycosaminoglycans. Org. Chem. Front. 2018, 5, 2685–91; https://doi.org/10.1039/c8qo00606g.Suche in Google Scholar
8. Yuan, D.; Yan, H.; Liu, J.; Liu, J.; Li, C.; Wang, J. A Fast and Colorimetric Sensor Array for the Discrimination of Ribonucleotides in Human Urine Samples by Gold Nanorods. Chin. Chem. Lett. 2020, 31, 455–8; https://doi.org/10.1016/j.cclet.2019.07.067.Suche in Google Scholar
9. Tian, J.-H.; Hu, X.-Y.; Hu, Z.-Y.; Tian, H.-W.; Li, J.-J.; Pan, Y.-C.; Li, H.-B.; Guo, D.-S. A Facile Way to Construct Sensor Array Library Via Supramolecular Chemistry for Discriminating Complex Systems. Nat. Commun. 2022, 13, 4293; https://doi.org/10.1038/s41467-022-31986-x.Suche in Google Scholar PubMed PubMed Central
10. Chen, L.; Yao, X.; Liu, X.; Luo, Z.; Ye, C.; Huang, C.; Wang, C.; Cai, C.; Lyu, L.; Wu, X.; Bi, H. High Throughput In-Situ Temperature Sensor Array with High Sensitivity and Excellent Linearity for Wireless Body Temperature Monitoring. Small Struct. 2022, 3, 2200080; https://doi.org/10.1002/sstr.202200080.Suche in Google Scholar
11. Hu, X.; Zhang, H.; Wang, Z.; Shiu, C. Y. A.; Gu, Z. Microneedle Array Patches Integrated with Nanoparticles for Therapy and Diagnosis. Small Struct. 2021, 2, 2000097; https://doi.org/10.1002/sstr.202000097.Suche in Google Scholar
12. Chen, F.; Qin, M.; Liu, W.; Wang, F.; Ren, W.; Xu, H.; Li, F. Snake Venom Identification via Fluorescent Discrimination. Anal. Chem. 2021, 93, 14025–30; https://doi.org/10.1021/acs.analchem.1c02804.Suche in Google Scholar PubMed
13. Pan, Y.-C.; Wang, H.; Xu, X.; Tian, H.-W.; Zhao, H.; Hu, X.-Y.; Zhao, Y.; Liu, Y.; Ding, G.; Meng, Q.; Ravoo, B. J.; Zhang, T.; Guo, D.-S. CCS Chem. 2020, 2, 2485–97.10.31635/ccschem.020.202000561Suche in Google Scholar
14. Xu, Z.; Jia, S.; Wang, W.; Yuan, Z.; Ravoo, B. J.; Guo, D.-S. Heteromultivalent Peptide Recognition by Co-Assembly of Cyclodextrin and Calixarene Amphiphiles Enables Inhibition of Amyloid Fibrillation. Nat. Chem. 2019, 11, 86–93; https://doi.org/10.1038/s41557-018-0164-y.Suche in Google Scholar PubMed
15. Hu, X.-Y.; Hu, Z.-Y.; Tian, J.-H.; Shi, L.; Ding, F.; Li, H.-B.; Guo, D.-S. A Heteromultivalent Host–Guest Sensor Array for Cell Recognition and Discrimination. Chem. Commun. 2022, 58, 13198–201; https://doi.org/10.1039/d2cc04963e.Suche in Google Scholar PubMed
16. Tian, H.-W.; Chang, Y.-X.; Hu, X.-Y.; Shah, M. R.; Li, H.-B.; Guo, D.-S. Supramolecular Imaging of Spermine in Cancer Cells. Nanoscale 2021, 13, 15362–8; https://doi.org/10.1039/d1nr04328e.Suche in Google Scholar PubMed
17. Gao, J.; Li, J.; Geng, W.-C.; Chen, F.-Y.; Duan, X.-C.; Zheng, Z.; Ding, D.; Guo, D.-S. Biomarker Displacement Activation: A General Host–Guest Strategy for Targeted Phototheranostics in Vivo. J. Am. Chem. Soc. 2018, 140, 4945–53; https://doi.org/10.1021/jacs.8b02331.Suche in Google Scholar PubMed
18. Tasoulis, T.; Isbister, G. K. A Review and Database of Snake Venom Proteomes. Toxins 2017, 9, 290; https://doi.org/10.3390/toxins9090290.Suche in Google Scholar PubMed PubMed Central
19. Hayashi, K.; Takechi, M.; Sasaki, T.; Lee, C. Y. Amino Acid Sequence of Cardiotoxin-Analogue I from the Venom of Naja Naja Atra. Biochem. Biophys. Res. Commun. 1975, 64, 360–6; https://doi.org/10.1016/0006-291x(75)90262-4.Suche in Google Scholar PubMed
20. Yang, C. C.; King, K.; Sun, T. P. Chemical Modification of Lysine and Histidine Residues in Phospholipase A2 from the Venom of Naja Naja Atra (Taiwan cobra). Toxicon 1981, 19, 645–59; https://doi.org/10.1016/0041-0101(81)90102-1.Suche in Google Scholar PubMed
21. Roly, Z. Y.; Islam, M. M.; Reza, M. A. A Comparative In Silico Characterization of Functional and Physicochemical Properties of 3FTx (Three Finger Toxin) Proteins from Four Venomous Snakes. Bioinformation 2014, 10, 281–7; https://doi.org/10.6026/97320630010281.Suche in Google Scholar PubMed PubMed Central
22. Garcia-Fernandez, R.; Peigneur, S.; Pons, T.; Alvarez, C.; Gonzalez, L.; Chavez, M. A.; Tytgat, J. The Kunitz-Type Protein ShPI-1 Inhibits Serine Proteases and Voltage-Gated Potassium Channels. Toxins 2016, 8, 110; https://doi.org/10.3390/toxins8040110.Suche in Google Scholar PubMed PubMed Central
23. Naghibi, S.; Chen, T.; Jamshidi Ghahfarokhi, A.; Tang, Y. AIEgen‐Enhanced Protein Imaging: Probe Design and Sensing Mechanisms. Aggregate 2021, 2, e41; https://doi.org/10.1002/agt2.41.Suche in Google Scholar
24. Song, B.-L.; Zhang, X.-H.; Qiao, Z.-Y.; Wang, H. Peptide-Based AIEgens: From Molecular Design, Stimuli Responsiveness to Biomedical Application. CCS Chem. 2022, 4, 437–55; https://doi.org/10.31635/ccschem.021.202101231.Suche in Google Scholar
25. Balachandran, Y. L.; Jiang, X. Aggregation-Induced Fluorogens in Bio-Detection, Tumor Imaging, and Therapy: A Review. CCS Chem. 2022, 4, 420–36; https://doi.org/10.31635/ccschem.021.202101307.Suche in Google Scholar
26. Borges, R. J.; Cardoso, F. F.; Fernandes, C. A. H.; Dreyer, T. R.; de Moraes, D. S.; Floriano, R. S.; Rodrigues-Simioni, L.; Fontes, M. R. M. Functional and Structural Studies of a Phospholipase A2-like Protein Complexed to Zinc Ions: Insights on its Myotoxicity and Inhibition Mechanism. Biochim. Biophys. Acta Gen. Subj. 2017, 1861, 3199–209; https://doi.org/10.1016/j.bbagen.2016.08.003.Suche in Google Scholar PubMed
27. Konshina, A. G.; Krylov, N. A.; Efremov, R. G. Cardiotoxins: Functional Role of Local Conformational Changes. J. Chem. Inf. Model. 2017, 57, 2799–810; https://doi.org/10.1021/acs.jcim.7b00395.Suche in Google Scholar PubMed
28. Tian, H.-W.; Xu, Z.; Li, H.-B.; Hu, X.-Y.; Guo, D.-S. Study on Assembling Compactness of Amphiphilic Calixarenes by Fluorescence Anisotropy. Supramol. Chem. 2022, 33, 527–33; https://doi.org/10.1080/10610278.2022.2087523.Suche in Google Scholar
29. Chen, J.; Liu, J.; Chen, X.; Qiu, H. Recent Progress in Nanomaterial-Enhanced Fluorescence Polarization/Anisotropy Sensors. Chin. Chem. Lett. 2019, 30, 1575–80; https://doi.org/10.1016/j.cclet.2019.06.005.Suche in Google Scholar
30. Popelka, S. R.; Miller, D. M.; Holen, J. T.; Kelso, D. M. Fluorescence Polarization Immunoassay. II. Analyzer for Rapid, Precise Measurement of Fluorescence Polarization with Use of Disposable Cuvettes. Clin. Chem. 1981, 27, 1198–201; https://doi.org/10.1093/clinchem/27.7.1198.Suche in Google Scholar
31. Georgieva, D.; Arni, R. K.; Betzel, C. Proteome Analysis of Snake Venom Toxins: Pharmacological Insights. Expert Rev. Proteomics 2008, 5, 787–97; https://doi.org/10.1586/14789450.5.6.787.Suche in Google Scholar PubMed
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/pac-2024-0320).
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