Tailoring Cationic Helical Polypeptides for Efficient Cytosolic Protein Delivery  

作　　者：WANG Ruijue SHENG Kai HOU Yingqin SUN Jialing LU Hua 

机构地区：[1]Beijing National Laboratory for Molecular Sciences,Center for Soft Matter Science and Engineering,Key Laboratory of Polymer Chemistry and Physics of Ministry of Education,College of Chemistry and Molecular Engineering,Peking University,Beijing 100871,P.R.China

出　　处：《Chemical Research in Chinese Universities》2020年第1期134-138,共5页高等学校化学研究（英文版）

基　　金：Supported by the National Key Research and Development Program of China(No.2016YFA0201400);the National Natural Science Foundation of China(Nos.21434008,21722401).

摘　　要：Protein delivery is of central importance for both diagnostic and therapeutic applications.However,protein delivery faces challenges including poor endosomal escape and thus limited efficiency.Here,we report the facile construction and screening of a small library of cationic helical polypeptides for cytosolic protein delivery.The library is based on a random copolymer poly(γ-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}esteryl-L-glutamate)-randompoly(γ-6-chlorohexyl-L-glutamate)[P(EG3-r-ClC6)Glu],which is then modified with various pyridine derivatives and alkyl thiols.Flow Cytometry,confocal laser scanning microscopy,and viability assay collaboratively identify two leading polymers,showing efficient delivery of enhanced green fluorescent protein(eGFP)and low cytoto-xicity.This finding is further validated by the cytosolic delivery of RNase A and cytochrome C(Cyt C)to HeLa cells in the viability assay.Together,this work demonstrates that high-throughput screening is an effective and viable approach to the selection of cationic helical polypeptides for the cytosolic delivery of functional proteins.

关 键 词：Cationic helical polypeptide Protein delivery Cytosolic protein 

分 类 号：O62[理学—有机化学]