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

作　　者：Weiyu Chen Zenghui Li Chenguang Zhao Lisha Zha Junfeng Shi Dan Yuan 

机构地区：[1]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 [2]Shenzhen Research Institute,Hunan University,Shenzhen 518000,China

出　　处：《Chinese Chemical Letters》2024年第12期245-248,共4页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.21975068);Natural Science Foundation of Hunan(No.2022JJ10008);Science and Technology and Development Foundation of Shenzhen(No.JCYJ20210324122403010);Natural Science Foundation of Changsha(No.kq2202152)。

摘　　要：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 bioactiveα-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.

关 键 词：Enzymatic action DEPHOSPHORYLATION Conformation shift Cell-penetrating peptide Selective delivery 

分 类 号：R943[医药卫生—药剂学]