Related Experiment Video
Updated: Nov 21, 2025
Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation
Published on: January 26, 2016
Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study
Francisco Ramos-Martín1, Nicola D'Amelio1
1Unité de Génie Enzymatique et Cellulaire UMR 7025 CNRS, Université de Picardie Jules Verne, 80039 Amiens, France.
Abstract:
Esophageal cancer is an aggressive lethal malignancy causing thousands of deaths every year. While current treatments have poor outcomes, cecropinXJ (CXJ) is one of the very few peptides with demonstrated in vivo activity. The great interest in CXJ stems from its low toxicity and additional activity against most ESKAPE bacteria and fungi. Here, we present the first study of its mechanism of action based on molecular dynamics (MD) simulations and sequence-property alignment. Although unstructured in solution, predictions highlight the presence of two helices separated by a flexible hinge containing P24 and stabilized by the interaction of W2 with target biomembranes: an amphipathic helix-I and a poorly structured helix-II. Both MD and sequence-property alignment point to the important role of helix I in both the activity and the interaction with biomembranes. MD reveals that CXJ interacts mainly with phosphatidylserine (PS) but also with phosphatidylethanolamine (PE) headgroups, both found in the outer leaflet of cancer cells, while salt bridges with phosphate moieties are prevalent in bacterial biomimetic membranes composed of PE, phosphatidylglycerol (PG) and cardiolipin (CL). The antibacterial activity of CXJ might also explain its interaction with mitochondria, whose phospholipid composition recalls that of bacteria and its capability to induce apoptosis in cancer cells.
Insights
CecropinXJ (CXJ) shows promise against esophageal cancer by interacting with cancer cell membranes. This peptide also exhibits antibacterial and antifungal properties, potentially offering a dual therapeutic approach.
Area of Science:
- Biochemistry
- Molecular Biology
- Computational Biophysics
Background:
- Esophageal cancer is a deadly malignancy with limited effective treatments.
- CecropinXJ (CXJ) is a peptide with demonstrated in vivo anticancer and antimicrobial activity.
- Understanding CXJ's mechanism of action is crucial for therapeutic development.
Purpose of the Study:
- To elucidate the mechanism of action of cecropinXJ (CXJ) against cancer cells.
- To investigate the interaction of CXJ with biomembranes using computational methods.
- To correlate structural features of CXJ with its biological activity.
Main Methods:
- Molecular dynamics (MD) simulations were employed to study CXJ behavior.
- Sequence-property alignment was used to analyze CXJ structure-activity relationships.
- Biomimetic membrane models were utilized to simulate interactions.
Main Results:
- CXJ possesses two helical structures, with helix I playing a key role in membrane interaction and activity.
- MD simulations revealed CXJ interacts with phosphatidylserine (PS) and phosphatidylethanolamine (PE) on cancer cell membranes.
- CXJ forms salt bridges with phosphate moieties in bacterial-like membranes, explaining its antimicrobial effects.
Conclusions:
- CXJ's interaction with cancer cell membrane lipids contributes to its efficacy.
- The peptide's structural and functional properties suggest potential as a dual-action therapeutic agent.
- CXJ's interaction with mitochondrial membranes may contribute to cancer cell apoptosis.
More Related Videos
08:31Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
10:13Production and Visualization of Bacterial Spheroplasts and Protoplasts to Characterize Antimicrobial Peptide Localization
Published on: August 11, 2018
