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Programme: SysMO2
Published year: 20112
Structural basis for the enhanced activity of cyclic antimicrobial peptides: The case of BPC194

Abstract (Expand)

We report the molecular basis for the differences in activity of cyclic and linear antimicrobial peptides. We iteratively performed atomistic molecular dynamics simulations and biophysical measurements … to probe the interaction of a cyclic antimicrobial peptide and its inactive linear analogue with model membranes. We establish that, relative to the linear peptide, the cyclic one binds stronger to negatively charged membranes. We show that only the cyclic peptide folds at the membrane interface and adopts a beta-sheet structure characterised by two turns. Subsequently, the cyclic peptide penetrates deeper into the bilayer while the linear peptide remains essentially at the surface. Finally, based on our comparative study, we propose a model characterising the mode of action of cyclic antimicrobial peptides. The results provide a chemical rationale for enhanced activity in certain cyclic antimicrobial peptides and can be used as a guideline for design of novel antimicrobial peptides.

Authors: , Gemma Moiset, Anna D Cirac, Lidia Feliu, Eduard Bardají, Marta Planas, Durba Sengupta, Siewert J Marrink,

Date Published: 19th May 2011

Publication Type: Not specified

The molecular basis for antimicrobial activity of pore-forming cyclic peptides

Abstract (Expand)

The mechanism of action of antimicrobial peptides is, to our knowledge, still poorly understood. To probe the biophysical characteristics that confer activity, we present here a molecular-dynamics and … biophysical study of a cyclic antimicrobial peptide and its inactive linear analog. In the simulations, the cyclic peptide caused large perturbations in the bilayer and cooperatively opened a disordered toroidal pore, 1-2 nm in diameter. Electrophysiology measurements confirm discrete poration events of comparable size. We also show that lysine residues aligning parallel to each other in the cyclic but not linear peptide are crucial for function. By employing dual-color fluorescence burst analysis, we show that both peptides are able to fuse/aggregate liposomes but only the cyclic peptide is able to porate them. The results provide detailed insight on the molecular basis of activity of cyclic antimicrobial peptides.

Authors: Anna D Cirac, Gemma Moiset, , Armagan Koçer, Pedro Salvador, , Siewert J Marrink, Durba Sengupta

Date Published: 18th May 2011

Publication Type: Not specified

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