Molecular Dynamics and Experimental Investigations of Membrane Perturbation by Ceragenin CSA-13R. Jueati, J. Jittikoon, O. Vajragupta, and J. Pimthon*
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Ceragenin CSA-13, a cholic acid derivative, has been reported as a novel template/scaffold for development of more potent and specific antibiotics. However, the exact mechanism of ceragenin CSA-13 action is not completely understood. This study aimed at investigating the molecular mechanism of membrane disruption by ceragenin CSA-13 using molecular dynamics (MD) simulations and experimental studies. Our findings showed that CSA-13 effectively induces calcein leakage when interacted with negatively charged DOPG vesicles, while exhibited weak dye-leakage activity for DOPC vesicles. The experimental results are very well in agreement with the MD calculations, where we observed the insertion of ceragenin CSA-13 molecules into PG bilayer membrane, induced an increase membrane fluidity and resulting in the membrane destabilization.
Keyword:
MD Simulation, cholic acid-derived antimicrobial agents, calcein leakage, lipid membranes, interaction
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