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Updated: Feb 28, 2026

Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
Published on: September 19, 2022
Trictide, a tricellulin-derived peptide to overcome cellular barriers
Jimmi Cording1, Basak Arslan1, Christian Staat1
1Department of Molecular Physiology and Cell Biology, Leibniz Institute of Molecular Pharmacology, Berlin, Germany.
Tricellulin peptides can open cellular barriers, increasing molecule passage. This discovery offers a novel approach for transiently enhancing drug delivery across tight junctions.
Area of Science:
- Cell Biology
- Biochemistry
- Drug Delivery
Background:
- Tight junctions (TJs) control paracellular permeability, with tricellulin (TCV) specifically sealing tricellular TJs (tTJs).
- Understanding how TJs are regulated is crucial for therapeutic applications, particularly for drug delivery.
Purpose of the Study:
- To investigate the effect of tricellulin extracellular loop 2 (ECL2) on cellular barriers.
- To explore the potential of a synthetic peptide derived from TCV ECL2, named trictide, in modulating TJ permeability.
Main Methods:
- Application of recombinant TCV ECL2 and synthetic trictide to human epithelial cells.
- Measurement of solute passage across cell layers.
- Super-resolution microscopy (STED) to visualize TJ protein localization.
- Fluorescence resonance energy transfer (FRET) to assess protein interactions.
- Circular dichroism spectroscopy and molecular modeling.
Main Results:
- Tricellulin ECL2 and trictide significantly increased the passage of ions and molecules up to 10 kDa.
- Tricellulin and lipolysis-stimulated lipoprotein receptor relocated from tTJs to bicellular TJs (bTJs), while claudin-1 and occludin moved to the cytosol.
- Microscopy revealed a tricellulin-free area at the tTJ region upon trictide treatment.
- Trictide disrupted cis-interactions between TJ proteins.
Conclusions:
- Trictide, a peptidomimetic of TCV ECL2, effectively opens both bTJs and tTJs.
- Trictide's mechanism involves altering TJ protein localization and interactions.
- This peptide represents a promising tool for transiently enhancing drug delivery by overcoming cellular barriers.
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