Label-free measurement of antimicrobial peptide interactions with lipid vesicles and nanodiscs using microscale thermophoresis.

One strategy to combat antimicrobial resistance is the discovery of new classes of antibiotics. Most antibiotics will at some point interact with the bacterial membrane to either interfere with its integrity or to cross it. Reliable and efficient tools for determining the dissociation constant for membrane binding (K) and the partitioning coefficient between the aqueous- and membrane phases (K) are therefore important tools for discovering and optimizing antimicrobial hits.

Goldilocks Dilemma: LPS Works Both as the Initial Target and a Barrier for the Antimicrobial Action of Cationic AMPs on .

Antimicrobial peptides (AMPs) are generally membrane-active compounds that physically disrupt bacterial membranes. Despite extensive research, the precise mode of action of AMPs is still a topic of great debate. This work demonstrates that the initial interaction between the Gram-negative and AMPs is driven by lipopolysaccharides (LPS) that act as kinetic barriers for the binding of AMPs to the bacterial membrane.

Guiding the Immune Response to a Conserved Epitope in MSP2, an Intrinsically Disordered Malaria Vaccine Candidate.

The malaria vaccine candidate merozoite surface protein 2 (MSP2) has shown promise in clinical trials and is in part responsible for a reduction in parasite densities. However, strain-specific reductions in parasitaemia suggested that polymorphic regions of MSP2 are immuno-dominant. One strategy to bypass the hurdle of strain-specificity is to bias the immune response towards the conserved regions.

Side-Chain Interactions in d/l Peptide Nanotubes: Studies by Crystallography, NMR Spectroscopy and Molecular Dynamics.

Our understanding of the factors affecting the stability of cyclic d/l peptide (CP) nanotubes remains underdeveloped. In this work, we investigate the impact of side chain alignment, hydrophobicity and charge on CP nanotube stability through X-ray crystallography, NMR spectroscopy and molecular dynamics (MD) simulations. We characterise the distinct CP-CP alignments that can form and identify stable and unstable dimers by MD simulation.

Controlled Construction of Cyclic d / l Peptide Nanorods.

Cyclic d / l peptides (CPs) assemble spontaneously via backbone H-bonding to form extended nanostructures. These modular materials have great potential as versatile bionanomaterials. However, the useful development of CP nanomaterials requires practical methods to direct and control their assembly.

Parallel and antiparallel cyclic d/l peptide nanotubes.

Nanotubes made from H-bonded cyclic d/l peptide (CP) subunits have great potential for the construction of nanomaterials of wide chemical and structural diversity but, to date, difficulties in structural characterisation have restricted development of these materials. We present the first crystal structures of continuous CP nanotubes with antiparallel and parallel stacking arrangements, assembled separately from two peptides; cyclo[(Asp-d-Leu-Lys-d-Leu)] and cyclo[(Asp-d-Ala-Lys-d-Ala)].