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Tailoring Cationic Helical Polypeptides for Efficient Cytosolic Protein Delivery

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Chemical Research in Chinese Universities Aims and scope

Abstract

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 cytotoxicity. 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.

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  1. Co-first author.

Authors and Affiliations

  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

    Ruijue Wang, Kai Sheng, Yingqin Hou, Jialing Sun & Hua Lu

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  1. Ruijue Wang
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  2. Kai Sheng
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  3. Yingqin Hou
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  4. Jialing Sun
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  5. Hua Lu
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Corresponding author

Correspondence to Hua Lu.

Additional information

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

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Wang, R., Sheng, K., Hou, Y. et al. Tailoring Cationic Helical Polypeptides for Efficient Cytosolic Protein Delivery. Chem. Res. Chin. Univ. 36, 134–138 (2020). https://doi.org/10.1007/s40242-019-0060-z

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  • DOI: https://doi.org/10.1007/s40242-019-0060-z

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