Related Experiment Video
Updated: May 12, 2026
21:08
Engineering Cell-permeable Protein
Published on: December 28, 2009
14.9K
Click-Cyclized Cell Penetrating Peptides Containing Hydrophobic Proline Derivatives for Efficient Intracellular
Yuan Zhang1, Jacob Kæstel-Hansen2, David Teze1
1Center for Evolutionary Chemical Biology, Department of Chemistry, University of Copenhagen, Copenhagen, DK-2100, Denmark.
Angewandte Chemie (International Ed. in English)
|November 17, 2025
Summary
Researchers developed a novel cyclic cell-penetrating peptide (cCPP 15) that efficiently delivers macromolecules, like proteins, into cells. This breakthrough offers a promising strategy for intracellular delivery, overcoming cell membrane impermeability challenges.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Intracellular delivery of macromolecules is hindered by cell membrane impermeability.
- Nanoparticles offer limited efficiency for protein delivery into cells.
- Cell-penetrating peptides (CPPs) are a versatile alternative for intracellular cargo transport.
Purpose of the Study:
- To develop novel cyclic CPPs with enhanced cell penetration capabilities.
- To investigate the impact of substituted prolines on CPP efficiency.
- To evaluate the intracellular delivery of macromolecules using modified CPPs.
Main Methods:
- Synthesized and tested 17 linear and click-cyclic CPPs with substituted prolines.
- Investigated the import of fluorophore ATOTA into MCF-7 and other cell lines.
- Utilized flow cytometry and spinning disk confocal microscopy for permeability analysis.
- Conjugated CPPs with enhanced green fluorescent protein (EGFP) for protein delivery studies.
Main Results:
- Cyclic cell-penetrating peptide 15 (cCPP 15) demonstrated remarkable cell permeability.
- cCPP 15 efficiently delivered enhanced green fluorescent protein (EGFP) into MCF-7 and HeLa cells.
- A specific modification in cCPP 15 significantly enhanced intracellular penetration.
Conclusions:
- Modified cyclic CPPs, particularly cCPP 15, show high efficiency for intracellular macromolecule delivery.
- This peptide represents a valuable tool for advancing intracellular delivery strategies.
- Potential applications include drug and protein delivery across biological barriers, including the blood-brain barrier.
Related Concept Videos
01:19Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
01:12Clathrin Coated Vesicles
Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
01:24Site-Targeted Drug Delivery Systems: Polymeric Carriers
Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...