Abstract

Cell-penetrating peptides show promise as versatile tools for intracellular delivery of therapeutic agents. Various peptides have originated from natural proteins with antimicrobial activity. We investigated the mammalian cell-penetrating properties of a 16-residue peptide with the sequence GRCRGFRRRCFCTTHC from the C-terminus tail of the Medicago truncatula defensin MtDef4. We evaluated the peptide’s ability to penetrate multiple cell types. Our results demonstrate that the peptide efficiently penetrates mammalian cells within minutes and at a micromolar concentration. Moreover, upon N-terminal fusion to the fluorescent protein GFP, the peptide efficiently delivers GFP into the cells. Despite its remarkable cellular permeability, the peptide has only a minor effect on cellular viability, making it a promising candidate for developing a cell-penetrating peptide with potential therapeutic applications.

Details

Title
Nature-inspired peptide of MtDef4 C-terminus tail enables protein delivery in mammalian cells
Author
Lifshits, Lucia Adriana 1 ; Breuer, Yoav 1 ; Sova, Marina 1 ; Gupta, Sumit 2 ; Kadosh, Dar 1 ; Weinberg, Evgeny 1 ; Hayouka, Zvi 3 ; Bar, Daniel Z. 1 ; Gal, Maayan 1 

 Tel Aviv University, Department of Oral Biology, Faculty of Medicine, The Goldschleger School of Dental Medicine, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546) 
 Tel-Aviv University, BLAVATNIK CENTER for Drug Discovery, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546) 
 The Hebrew University of Jerusalem, Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agricultural, Food and Environment, Rehovot, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538) 
Pages
4604
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3048741590
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.