Exploring the Membrane Mechanism of the Bioactive Peptaibol Ampullosporin A Using Lipid Monolayers and Supported Biomimetic Membranes

Abstract

Ampullosporin A is an antimicrobial, neuroleptic peptaibol, the behavior of which was investigated in different membrane mimetic environments made of egg yolk L-α-phosphatidylcholine. In monolayers, the peptaibol adopted a mixed α/310-helical structure with an in-plane orientation. The binding step was followed by the peptide insertion into the lipid monolayer core. The relevance of the inner lipid leaflet nature was studied by comparing ampullosporin binding on a hybrid bilayer, in which this leaflet was a rigid alkane layer, and on supported fluid lipid bilayers. The membrane binding was examined by surface plasmon resonance spectroscopy and the effect on lipid dynamics was explored using fluorescence recovery after photobleaching. In the absence of voltage and at low concentration, ampullosporin A substantially adsorbed onto lipid surfaces and its interaction with biomimetic models was strongly modified depending on the inner leaflet structure. At high concentration, ampullosporin A addition led to the lipid bilayers disruption.

EGFR Inhibition by Curcumin in Cancer Cells: A Dual Mode of Action

“…The value of the lateral coefficient in the absence of lipids is consistent with the previously published data for SLB of the same lipid composition. 56,57 Curcumin significantly decreases lipid lateral diffusion at concentration above 0.4 µM. Together with the fluorescence anisotropy data, these findings confirm the proposed scenario of the rigidification of the membrane by curcumin.…”

Length-Dependent Formation of Transmembrane Pores by 310-Helical α-Aminoisobutyric Acid Foldamers

“…The HPTS assay cannot easily discriminate between ion channel/pore, , membrane disruption, and ion carrier mechanisms, all of which have been suggested to occur for the structurally related peptaibols. An ion carrier mechanism for Na + transport by this family of foldamers was discounted as no activity was observed over 20 h for 1 , 7 , and 8 in simple U-tube assays (see the Supporting Information).…”

Synthesis and conformational properties of a TOAC doubly spin‐labeled analog of the medium‐length, membrane active peptaibiotic ampullosporin a as revealed by cd, fluorescence, and EPR spectroscopies

“…Ampullosporins display moderate antibacterial and antifungal activities . However, other interesting biochemical (e.g., induction of fungal pigment formation and hypothermia, and inhibition of locomotion in mice) and biophysical properties have been documented . In general, the residues of the molecule most critical for the biophysical and biological activities include an N‐terminal Ac‐aromatic amino acid unit and the triplet of consecutive C α ‐tetrasubstituted amino acids at positions 8–10 (particularly effective seems to be the Aib residue at position 9, which can be replaced without detrimental effects only by an amino acid of the same class, e.g., 1‐amino‐1‐cyclohexane carboxylic acid).…”