Nature-inspired peptide of MtDef4 C-terminus tail enables protein delivery in mammalian cells

Lucia Adriana Lifshits, Yoav Breuer, Marina Sova, Sumit Gupta, Dar Kadosh, Evgeny Weinberg, Zvi Hayouka, Daniel Z. Bar, Maayan Gal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageAmerican English
Article number4604
JournalScientific Reports
Volume14
Issue number1
DOIs
StatePublished - Dec 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Keywords

  • Cell-penetrating peptide (CPP)
  • Cellular uptake
  • Delivery agents
  • MtDef4
  • Peptides
  • Protein transduction
  • Therapeutics

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