Citation: Weiyu Chen, Zenghui Li, Chenguang Zhao, Lisha Zha, Junfeng Shi, Dan Yuan. Enzyme-modulate conformational changes in amphiphile peptide for selectively cell delivery[J]. Chinese Chemical Letters, ;2024, 35(12): 109628. doi: 10.1016/j.cclet.2024.109628 shu

Enzyme-modulate conformational changes in amphiphile peptide for selectively cell delivery

Weiyu Chen ^{a, b, 1} ,
Zenghui Li ^{a, b, 1} ,
Chenguang Zhao ^{a, b} ,
Lisha Zha ^{a, *,} ,
Junfeng Shi ^{a, b, *,} ,
Dan Yuan ^{a, b, *,}

a.
Hunan Provincial Key Laboratory of Animal Models and Molecular Medicine, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, School of Biomedical Sciences, Hunan University, Changsha 410082, China
b.
Shenzhen Research Institute, Hunan University, Shenzhen 518000, China

zhalisha@hnu.edu.cn

jeff-shi@hnu.edu.cn

yuandan@hnu.edu.cn

Received Date: 14 December 2023
Revised Date: 5 February 2024
Accepted Date: 6 February 2024
Available Online: 9 February 2024

Figures(4)

Achieving selectivity in cell penetrating peptide (CPP) design is crucial to mitigate systemic toxicity and enable precise targeting based on distinct cellular phenotypes. Herein, we designed an amphiphilic peptide, L17Yp, by incorporating phosphorylated tyrosine into natural occurring M-lycotoxin peptide, known for its potent membrane-lytic activity. This strategic modification induced a conformational shift, as confirmed by circular dichroism spectroscopy, transitioning it from its bioactive α-helix conformation to an inactive random coli configuration, effectively shielding its membrane-penetrating capacity. Upon exposure to alkaline phosphatase, L17Yp undergoes enzymatic dephosphorylation, prompting a conformational shift that restores its membrane-transduction capabilities. This unique property hold promises for selective drug delivery. This work introduces an enzymatic approach for targeted perturbation of the cell membrane, offering promising prospects for precise drug delivery applications.
- Enzymatic action,
- Dephosphorylation,
- Conformation shift,
- Cell-penetrating peptide,
- Selective delivery
1. [1]
  P. Lundberg, Ü. Langel, J. Mol. Recognit. 16 (2003) 227–233. doi: 10.1002/jmr.630
2. [2]
  R. Tian, H. Wang, R. Niu, et al., Adv. Colloid Interface Sci. 453 (2015) 15–20. doi: 10.1016/j.jcis.2015.04.028
3. [3]
  Y. Qin, Q. Guo, S. Wu, et al., Chin. Chem. Lett. 31 (2020) 3121–3126. doi: 10.1016/j.cclet.2020.06.023
4. [4]
  X. Fu, G. Zhang, Y. Zhang, et al., Chin. Chem. Lett. 32 (2021) 1559–1562. doi: 10.1016/j.cclet.2020.10.011
5. [5]
  X. Qin, H. Zhao, Y. Jiang, et al., Chin. Chem. Lett. 29 (2018) 1160–1162. doi: 10.1016/j.cclet.2018.04.004
6. [6]
  J. Zhou, Y. Cai, T. Li, et al., Small 20 (2024) 2302765. doi: 10.1002/smll.202302765
7. [7]
  O. Tietz, F. Cortezon-Tamarit, R. Chalk, et al., Nat. Chem. 14 (2022) 284–293. doi: 10.1038/s41557-021-00866-0
8. [8]
  J.V.V. Arafiles, J. Franke, L. Franz, et al., J. Am. Chem. Soc. 145 (2023) 24535–24548.
9. [9]
  H.D. Herce, D. Schumacher, A.F.L. Schneider, et al., Nat. Chem. 9 (2017) 762–771. doi: 10.1038/nchem.2811
10. [10]
  T. Lehto, K. Kurrikoff, Ü. Langel, Expert Opin. Drug Deliv. 9 (2012) 823–836. doi: 10.1517/17425247.2012.689285
11. [11]
  Y. Wang, C.H. Liu, T. Ji, et al., Nat. Commun. 10 (2019) 804. doi: 10.1038/s41467-019-08690-4
12. [12]
  H. He, J. Guo, B. Xu, ChemNanoMat 7 (2021) 1104–1107. doi: 10.1002/cnma.202100249
13. [13]
  Y. Cui, T. Zhu, X. Zhang, et al., Chin. Chem. Lett. 33 (2022) 4617–4622. doi: 10.1016/j.cclet.2022.03.077
14. [14]
  M. Zorko, Ü. Langel, Adv. Drug Deliv. Rev. 57 (2005) 529–545. doi: 10.1016/j.addr.2004.10.010
15. [15]
  C. Wu, Y. Li, Z. Cheng, et al., Chin. Chem. Lett. 33 (2022) 4339–4344. doi: 10.1016/j.cclet.2022.01.036
16. [16]
  H. Zhang, Q. Zhao, S. Bhattacharya, et al., J. Mol. Biol. 378 (2008) 565–580. doi: 10.1016/j.jmb.2008.02.066
17. [17]
  S. Chou, C. Shao, J. Wang, et al., Acta Biomater. 30 (2016) 78–93. doi: 10.1016/j.actbio.2015.11.002
18. [18]
  S.H. Medina, J.P. Schneider, J. Control. Release 209 (2015) 317–326. doi: 10.1016/j.jconrel.2015.05.267
19. [19]
  N. Safa, J.C. Anderson, M. Vaithiyanathan, et al., Pept. Sci. 111 (2019) e24092. doi: 10.1002/pep2.24092
20. [20]
  A. Walrant, S. Cardon, F. Burlina, et al., Acc. Chem. Res. 50 (2017) 2968–2975. doi: 10.1021/acs.accounts.7b00455
21. [21]
  A. Komin, M.I. Bogorad, R. Lin, et al., J. Control. Release 324 (2020) 633–643. doi: 10.1016/j.jconrel.2020.05.030
22. [22]
  P.E.G. Thorén, D. Persson, E.K. Esbjörner, et al., Biochemistry 43 (2004) 3471–3489. doi: 10.1021/bi0360049
23. [23]
  Y. Huang, Y. Jiang, H. Wang, et al., Adv. Drug Deliv. Rev. 65 (2013) 1299–1315. doi: 10.1016/j.addr.2012.11.007
24. [24]
  R. Sawant, V. Torchilin, Mol. Syst. Biol. 6 (2010) 628–640.
25. [25]
  K. Kardani, A. Milani, S.H. Shabani, et al., Expert Opin. Drug Deliv. 16 (2019) 1227–1258. doi: 10.1080/17425247.2019.1676720
26. [26]
  R. Morán-Torres, D.A. Castillo González, M.L. Durán-Pastén, et al., Pharmaceutics 13 (2021) 1119. doi: 10.3390/pharmaceutics13081119
27. [27]
  Q. Zhang, J. Tang, L. Fu, et al., Biomaterials 34 (2013) 7980–7993. doi: 10.1016/j.biomaterials.2013.07.014
28. [28]
  H. He, L. Sun, J. Ye, et al., J. Control. Release 240 (2016) 67–76. doi: 10.1016/j.jconrel.2015.10.040
29. [29]
  E. Vivès, J. Schmidt, A. Pèlegrin, Biochim. Biophys. Acta 1786 (2008) 126–138.
30. [30]
  F. Guo, Q. Fu, K. Zhou, et al., J. Nanobiotechnol. 18 (2020) 48. doi: 10.1186/s12951-020-00595-5
31. [31]
  J. Shi, J.P. Schneider, Angew. Chem. Int. Ed. 58 (2019) 13706–13710. doi: 10.1002/anie.201902470
32. [32]
  J. Li, F. Liu, Q. Shao, et al., Adv. Healthc. Mater. 3 (2014) 1230–1239. doi: 10.1002/adhm.201300613
33. [33]
  J. Shi, X. Du, D. Yuan, et al., Biomacromolecules 15 (2014) 3559–3568. doi: 10.1021/bm5010355
34. [34]
  H. Wang, Z. Feng, D. Wu, et al., J. Am. Chem. Soc. 138 (2016) 10758–10761. doi: 10.1021/jacs.6b06075
35. [35]
  W. Tan, Q. Zhang, J. Wang, et al., Angew. Chem. Int. Ed. 60 (2021) 12796–12801. doi: 10.1002/anie.202102601
36. [36]
  J. Gao, J. Zhan, Z. Yang, Adv. Mater. 32 (2020) 1805798. doi: 10.1002/adma.201805798
37. [37]
  E. Eiríksdóttir, K. Konate, Ü. Langel, et al., Biochim. Biophys. Acta Bioenerg. 1798 (2010) 1119–1128. doi: 10.1016/j.bbamem.2010.03.005
38. [38]
  M. Xiong, Y. Bao, X. Xu, et al., Proc. Natl. Acad. Sci. U. S. A. 114 (2017) 12675–12680. doi: 10.1073/pnas.1710408114
39. [39]
  M. Akishiba, T. Takeuchi, Y. Kawaguchi, et al., Nat. Chem. 9 (2017) 751–761. doi: 10.1038/nchem.2779
40. [40]
  J. Han, B. Yong, C. Luo, et al., World J. Surg. Oncol. 10 (2012) 37. doi: 10.1186/1477-7819-10-37
41. [41]
  E. Murray, D. Provvedini, D. Curran, et al., J. Bone Miner. Res. 2 (1987) 231–238. doi: 10.1002/jbmr.5650020310
42. [42]
  H.A. Lagassé, A. Alexaki, V.L. Simhadri, et al., F1000Res. 6 (2017) 113. doi: 10.12688/f1000research.9970.1
43. [43]
  S. Reissmann, J. Pept. Sci. 20 (2014) 760–784. doi: 10.1002/psc.2672
44. [44]
  S. Chen, Z. Li, C. Zhang, et al., Small 19 (2023) 2301063. doi: 10.1002/smll.202301063
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沈阳化工大学材料科学与工程学院沈阳 110142