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
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沈阳化工大学材料科学与工程学院沈阳 110142