Citation: Fukui Shen, Yuqing Zhang, Guoqing Luan, Kaixue Zhang, Zhenzhen Wang, Yunhao Luo, Yuanyuan Hou, Gang Bai. Revealing drug targets with multimodal bioorthogonal AMPD probes through visual metabolic labeling[J]. Chinese Chemical Letters, ;2024, 35(12): 109646. doi: 10.1016/j.cclet.2024.109646 shu

Revealing drug targets with multimodal bioorthogonal AMPD probes through visual metabolic labeling

Fukui Shen ^a ,
Yuqing Zhang ^b ,
Guoqing Luan ^a ,
Kaixue Zhang ^a ,
Zhenzhen Wang ^a ,
Yunhao Luo ^a ,
Yuanyuan Hou ^{a, *,} ,
Gang Bai ^{a, *,}

a.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China
b.
College of Life Sciences, Nankai University, Tianjin 300071, China

houyy@nankai.edu.cn

gangbai@nankai.edu.cn

Received Date: 14 December 2023
Revised Date: 31 January 2024
Accepted Date: 3 February 2024
Available Online: 13 February 2024

Figures(5)

Multimodal bioorthogonal small molecule probes play a pivotal role in drug-focused biomedical research. However, existing drug tracking and imaging techniques face obstacles in living organisms, hindering precise drug localization and target protein capture. Herein, we introduced a multimodal probe named 1-(azidomethyl)pyrene-4,5–dione (AMPD). The probe incorporates adjacent dione structures at the pyrene core. AMPD selectively interacts with oxygen-rich alkene-labeled drug molecules under ice-blue LED light exposure, producing specific fluorescence emission and enabling in vivo tracking and flow cytometry sorting. A methyl azide group was also introduced at the pyrene core to help efficiently enrich target proteins via click chemistry with alkyne-functionalized beads. AMPD demonstrates exceptional biocompatibility, rendering it highly suitable for visual photo-triggered tracking studies. Combined with metabolic labeling using an oxygen-rich alkene-tagged drug molecule probe, AMPD is effective for live animal, tissue, cellular, and in-gel imaging, as well as target protein identification through magnetic capture. With its versatile capabilities, AMPD enhances our comprehension of drug-target interactions at the in vivo level and expedites the process of drug discovery.
- Multimodal bioorthogonal probe,
- Bioorthogonal reactions,
- Photoclick,
- In-situ,
- Drug tracking
1. [1]
  S.M. Hacker, C. Jessen-Trefzer, Biol. Chem. 403 (2022) 361–362. doi: 10.1515/hsz-2022-0119
2. [2]
  L.H. Jones, C. Heinis, Eur. J. Med. Chem. 88 (2014) 1–2. doi: 10.1016/j.ejmech.2014.10.017
3. [3]
  C. Borsari, D.J. Trader, A. Tait, M.P. Costi, J. Med. Chem. 63 (2020) 1908–1928. doi: 10.1021/acs.jmedchem.9b01456
4. [4]
  J.T. Du, J. Guo, D.W. Kang, et al., Chin. Chem. Lett. 31 (2020) 1695–1708. doi: 10.1016/j.cclet.2020.03.028
5. [5]
  Y.H. Zhang, H.Y. Xia, M.D. Yang, et al., Chin. Chem. Lett. 34 (2023) 108197. doi: 10.1016/j.cclet.2023.108197
6. [6]
  J.R. Shewring, A.J. Cankut, L.K. McKenzie, et al., Inorg. Chem. 56 (2017) 15259–15270. doi: 10.1021/acs.inorgchem.7b02633
7. [7]
  P. Shieh, C.R. Bertozzi, Org. Biomol. Chem. 12 (2014) 9307–9320. doi: 10.1039/C4OB01632G
8. [8]
  Y.Y. Liao, Y.T. Liang, Y.R. Huang, et al., Chin. Chem. Lett. 35 (2024) 109092. doi: 10.1016/j.cclet.2023.109092
9. [9]
  Y.L. Ma, S. Yan, X.J. Xu, et al., Chin. Chem. Lett. 35 (2024) 108645. doi: 10.1016/j.cclet.2023.108645
10. [10]
  M. Pretze, M. Kuchar, R. Bergmann, et al., ChemMedChem 8 (2013) 935–945. doi: 10.1002/cmdc.201300053
11. [11]
  Y.H. Shen, A.M. Esper, I. Ghiviriga, et al., Dalton Trans. 50 (2021) 12681–12691. doi: 10.1039/D1DT02626G
12. [12]
  M. Handula, K.T. Chen, Y. Seimbille, Molecules 26 (2021) 4640. doi: 10.3390/molecules26154640
13. [13]
  J. Miguel-Avila, M. Tomás-Gamasa, J.L. Mascareñas, Trends Chem. 5 (2023) 474–485. doi: 10.1016/j.trechm.2023.04.001
14. [14]
  A.D. Roses, Nat. Rev. Drug Discov. 7 (2008) 807–817. doi: 10.1038/nrd2593
15. [15]
  E. Coy-Barrera, I.V. Ogungbe, T.J. Schmidt, Molecules 28 (2023) 3690. doi: 10.3390/molecules28093690
16. [16]
  P. Neuzi, S. Giselbrecht, K. Lange, et al., Nat. Rev. Drug Discov. 11 (2012) 620–632. doi: 10.1038/nrd3799
17. [17]
  Y.S. Ren, H.L. Li, X.H. Piao, et al., Biochem. Pharmacol. 194 (2021) 114798. doi: 10.1016/j.bcp.2021.114798
18. [18]
  J. Venegas-Molina, P. Van Damme, A. Goossens, Methods Mol. Biol. 2554 (2023) 47–67.
19. [19]
  M. Pepelnjak, N. de Souza, P. Picotti, Trends Biochem. Sci. 45 (2020) 919–920. doi: 10.1016/j.tibs.2020.05.006
20. [20]
  M.A. Geer, M.C. Fitzgerald, J. Am. Soc. Mass Spectrom. 27 (2016) 233–243. doi: 10.1007/s13361-015-1290-z
21. [21]
  S. Ramachandran, M. Szewczyk, S.H. Barghout, et al., Methods Mol. Biol. 2706 (2023) 149–165.
22. [22]
  G.J. Tan, S.U. Berlangieri, S.T. Lee, A.M. Scott, Abdom. Imaging 39 (2014) 187–195. doi: 10.1007/s00261-013-0043-3
23. [23]
  C.C.L. Cheung, G. Ma, K. Karatasos, et al., Nanotheranostics 4 (2020) 91–106. doi: 10.7150/ntno.41737
24. [24]
  M. Bio, G. Nkepang, Y. You, Chem. Commun. 48 (2012) 6517–6519. doi: 10.1039/c2cc32373g
25. [25]
  G.S. Kumar, Q. Lin, Chem. Rev. 121 (2021) 6991–7031. doi: 10.1021/acs.chemrev.0c00799
26. [26]
  X. Ji, Z. Zhong, J. Control. Release 351 (2022) 81–101. doi: 10.1016/j.jconrel.2022.09.026
27. [27]
  S.L. Scinto, D.A. Bilodeau, R. Hincapie, et al., Nat. Rev. Methods Prim. 1 (2021) 30. doi: 10.1038/s43586-021-00028-z
28. [28]
  N.K. Devaraj, ACS Cent. Sci. 4 (2018) 952–959. doi: 10.1021/acscentsci.8b00251
29. [29]
  J. Wang, X. Wang, X.Y. Fan, P.R. Chen, ACS Cent. Sci. 7 (2021) 929–943. doi: 10.1021/acscentsci.1c00124
30. [30]
  S.S. Nguyen, J.A. Prescher, Nat. Rev. Chem. 4 (2020) 476–489. doi: 10.1038/s41570-020-0205-0
31. [31]
  H.B. Sun, Q.H. Xue, C. Zhang, et al., Org. Chem. Front. 9 (2022) 481–498. doi: 10.1039/D1QO01324F
32. [32]
  R. Gostl, A. Senf, S. Hecht, Chem. Soc. Rev. 43 (2014) 1982–1996. doi: 10.1039/c3cs60383k
33. [33]
  Z.M. Salimo, M.N. Yakubu, E.L. da Silva, et al., Biomolecules 13 (2023) 403. doi: 10.3390/biom13030403
34. [34]
  Z. Li, L. Qian, L. Li, et al., Angew. Chem. Int. Ed. 55 (2016) 3254-3254. doi: 10.1002/anie.201600314
35. [35]
  Y. Tian, M.P. Jacinto, Y. Zeng, et al., J. Am. Chem. Soc. 139 (2017) 6078–6081. doi: 10.1021/jacs.7b02615
36. [36]
  M. Zhang, X. Ma, H. Xu, et al., FEBS J. 287 (2020) 1816–1829. doi: 10.1111/febs.15112
37. [37]
  L. de Almeida, S. Devi, M. Indramohan, et al., Front. Immunol. 13 (2022) 912069. doi: 10.3389/fimmu.2022.912069
38. [38]
  X. Chen, Q. Wu, P. Depeille, et al., Cancer Cell 31 (2017) 685–696 e686. doi: 10.1016/j.ccell.2017.04.002
39. [39]
  S. Tang, T. Chen, Z. Yu, et al., Nat. Commun. 5 (2014) 4657. doi: 10.1038/ncomms5657
40. [40]
  D. Lei, Y. Sun, J. Liu, J. Chi, Ann. Transl. Med. 10 (2022) 1058. doi: 10.21037/atm-22-3781
41. [41]
  Q. Tang, Q. Wang, Z. Sun, et al., Front. Pharmacol. 12 (2021) 651664. doi: 10.3389/fphar.2021.651664
42. [42]
  Y. Quan, P. Su, C. Shangguan, et al., Toxicol. Appl. Pharmacol. 475 (2023) 116633. doi: 10.1016/j.taap.2023.116633
43. [43]
  H. Zhang, J.P. Wong, G. Ni, et al., PLoS Pathog. 18 (2022) e1010990. doi: 10.1371/journal.ppat.1010990
44. [44]
  X. Zhang, F. Zhang, F. Yao, et al., Neuroreport 33 (2022) 549–560. doi: 10.1097/WNR.0000000000001789
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沈阳化工大学材料科学与工程学院沈阳 110142