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

## TL;DR

A natural peptide from a plant protein can efficiently deliver molecules into mammalian cells without harming them.

## Contribution

A 16-residue peptide from the C-terminus of MtDef4 shows efficient mammalian cell penetration and delivery of GFP.

## Key findings

- The peptide efficiently penetrates mammalian cells within minutes at micromolar concentrations.
- The peptide can deliver fluorescent protein GFP into cells when fused at the N-terminus.
- The peptide has minimal impact on cell viability despite its high permeability.

## 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.