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


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 languageEnglish
Article number4604
JournalScientific Reports
Issue number1
StatePublished - Dec 2024


FundersFunder number
Adama Center
Bountica Ltd
Gertner Institute for Medical Nano System
Gertner Institute for the Medical Nano System29663
Israel Science FoundationISF 632/20
Tel Aviv University


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


    Dive into the research topics of 'Nature-inspired peptide of MtDef4 C-terminus tail enables protein delivery in mammalian cells'. Together they form a unique fingerprint.

    Cite this