Lipid oxidation controls peptide self-assembly near membranes through a surface attraction mechanism.

The self-assembly of peptides into supramolecular structures has been linked to neurodegenerative diseases but has also been observed in functional roles. Peptides are physiologically exposed to crowded environments of biomacromolecules, and particularly cellular membrane lipids. Previous research has shown that membranes can both accelerate and inhibit peptide self-assembly.

Interactions of Non-steroidal Anti-inflammatory Drugs and Their Bismuth Analogues (BiNSAIDs) with Biological Membrane Mimics at Physiological pH.

Previous studies have demonstrated the potential for non-steroidal anti-inflammatory drugs (NSAIDs), in particular aspirin, to be used as chemopreventives for colorectal cancer; however, a range of unwanted gastrointestinal side effects limit their effectiveness. Due to the role of bismuth in the treatment of gastrointestinal disorders, it is hypothesized that bismuth-coordinated NSAIDs (BiNSAIDs) could be used to combat the gastrointestinal side effects of NSAIDs while still maintaining their chemopreventive potential. To further understand the biological activity of these compounds, the present study examined four NSAIDs, namely, tolfenamic acid (tolfH), aspirin (aspH), indomethacin (indoH), and mefenamic acid (mefH) and their analogous homoleptic BiNSAIDs ([Bi(L)]), to determine how these compounds interact with biological membrane mimics composed of 1-palmitoyl-2-oleoyl--glycero-3-phosphocholine (POPC) or a mixture of POPC and cholesterol.

Comparing Surfactant Structures at "Soft" and "Hard" Hydrophobic Materials: Not All Interfaces Are Equivalent.

The interfacial structures of a range of amphiphilic molecules are studied with both "soft" and "hard" hydrophobic substrates. Neutron reflection and quartz crystal microbalance with dissipation measurements highlight the differences between the adsorbed structures adopted by sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and the "AM1" surface active peptide. At the soft siloxane/water interface, small molecular surfactants form loosely packed layers, with the hydrophobic tails penetrating into the oily layer, and an area per surfactant molecule that is significantly less than previously reported for the air/water interface.

Insights into the interfacial structure-function of poly(ethylene glycol)-decorated peptide-stabilised nanoscale emulsions.

The interfacial properties of nanoscale materials have profound influence on biodistribution and stability as well as the effectiveness of sophisticated surface-encoded properties such as active targeting to cell surface receptors. Tailorable nanocarrier emulsions (TNEs) are a novel class of oil-in-water emulsions stabilised by molecularly-engineered biosurfactants that permit single-pot stepwise surface modification with related polypeptides that may be chemically conjugated or genetically fused to biofunctional moieties. We have probed the structure and function of poly(ethylene glycol) (PEG) used to decorate TNEs in this way.

N-Terminal Ile-Orn- and Trp-Orn-Motif Repeats Enhance Membrane Interaction and Increase the Antimicrobial Activity of Apidaecins against Pseudomonas aeruginosa.

The Gram-negative bacterium Pseudomonas aeruginosa is a life-threatening nosocomial pathogen due to its generally low susceptibility toward antibiotics. Furthermore, many strains have acquired resistance mechanisms requiring new antimicrobials with novel mechanisms to enhance treatment options. Proline-rich antimicrobial peptides, such as the apidaecin analog Api137, are highly efficient against various Enterobacteriaceae infections in mice, but less active against P.

Analysis of Perforin Assembly by Quartz Crystal Microbalance Reveals a Role for Cholesterol and Calcium-independent Membrane Binding.

Perforin is an essential component in the cytotoxic lymphocyte-mediated cell death pathway. The traditional view holds that perforin monomers assemble into pores in the target cell membrane via a calcium-dependent process and facilitate translocation of cytotoxic proteases into the cytoplasm to induce apoptosis. Although many studies have examined the structure and role of perforin, the mechanics of pore assembly and granzyme delivery remain unclear.

Vesicular disruption of lysosomal targeting organometallic polyarginine bioconjugates.

Compounds which are able to destabilize the lysosomal membrane have been proposed as interesting candidates for targeted anticancer drugs due to the pronounced lysosomal changes in cancer cells. For this purpose, metallocene derivatives of a cell penetrating polyarginine peptide M–(Arg)9(Phe)2Lys–NH2 (where M = ferrocene carboxylate or ruthenocene carboxylate) were designed and their biological activities were investigated in detail. The ferrocenoyl- and ruthenocenoyl polyarginine bioconjugates were synthesized via Fmoc solid-phase peptide synthesis (SPPS) protocols on a microwave-assisted synthesizer.

Api88 is a novel antibacterial designer peptide to treat systemic infections with multidrug-resistant Gram-negative pathogens.

The emergence of multiple-drug-resistant (MDR) bacterial pathogens in hospitals (nosocomial infections) presents a global threat of growing importance, especially for Gram-negative bacteria with extended spectrum β-lactamase (ESBL) or the novel New Delhi metallo-β-lactamase 1 (NDM-1) resistance. Starting from the antibacterial peptide apidaecin 1b, we have optimized the sequence to treat systemic infections with the most threatening human pathogens, such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. The lead compound Api88 enters bacteria without lytic effects at the membrane and inhibits chaperone DnaK at the substrate binding domain with a K(D) of 5 μmol/L.

A mechanistic investigation of cell-penetrating Tat peptides with supported lipid membranes.

The multifarious Tat peptide derived from the HIV-1 virus exhibits antimicrobial activity. In this article, we use Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) to investigate the mechanisms of action of Tat (44-57) and Tat (49-57) on bacterial-mimetic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (sodium salt) (DMPG) membranes. The results reveal that both peptides disrupt DMPC/DMPG membranes via a surface-active (carpet-like) mechanism.

QCM-D fingerprinting of membrane-active peptides.

The increasing prevalence of antibiotic-resistant bacteria is becoming a public health crisis. Antimicrobial peptides (AMPs) are a promising solution, because bacterial resistance is less likely. Quartz crystal microbalance with dissipation monitoring (QCM-D) is a versatile and valuable technique for investigation of these peptides.

Oncocin (VDKPPYLPRPRPPRRIYNR-NH2): a novel antibacterial peptide optimized against gram-negative human pathogens.

Small proline-rich antimicrobial peptides (AMP) have attracted considerable interest, as they target specific intracellular bacterial components and do not act by lytic mechanisms. Here, a novel peptide, termed oncocin (VDKPPYLPRPRPPRRIYNR-NH(2)), is reported that was optimized for the treatment of Gram-negative pathogens. Its minimal inhibitory concentrations in tryptic soy broth medium ranged from 0.

Structure and homogeneity of pseudo-physiological phospholipid bilayers and their deposition characteristics on carboxylic acid terminated self-assembled monolayers.

Supported phospholipid bilayers are frequently used to establish a pseudo-physiological environment required for the study of protein function or the design of enzyme-based biosensors and biocatalytic reactors. These membranes are deposited from bilayer vesicles (liposomes) that rupture and fuse into a planar membrane upon adhesion to a surface. However, the morphology and homogeneity of the resulting layer is affected by the characteristics of the precursor liposome suspension and the substrate.