Delivery of siRNA Complexed with Palmitoylated α-Peptide/β-Peptoid Cell-Penetrating Peptidomimetics: Membrane Interaction and Structural Characterization of a Lipid-Based Nanocarrier System.

Proteolytically stable α-peptide/β-peptoid peptidomimetics constitute promising cell-penetrating carrier candidates exhibiting superior cellular uptake as compared to commonly used cell-penetrating peptides (CPPs). The aim of the present study was to explore the potential of these peptidomimetics for delivery of small interfering RNA (siRNA) to the cytosol by incorporation of a palmitoylated peptidomimetic construct into a cationic lipid-based nanocarrier system. The optimal construct was selected on the basis of the effect of palmitoylation and the influence of the length of the peptidomimetic on the interaction with model membranes and the cellular uptake.

Selectivity in the potentiation of antibacterial activity of α-peptide/β-peptoid peptidomimetics and antimicrobial peptides by human blood plasma.

Antimicrobial peptides (AMPs) are promising leads for novel antibiotics; however, their activity is often compromised under physiological conditions. The purpose of this study was to determine the activity of α-peptide/β-peptoid peptidomimetics and AMPs against Escherichia coli and Staphylococcus aureus in the presence of human blood-derived matrices and immune effectors. The minimum inhibitory concentration (MIC) of two peptidomimetics against E.

High in vitro antimicrobial activity of β-peptoid-peptide hybrid oligomers against planktonic and biofilm cultures of Staphylococcus epidermidis.

An array of β-peptoid-peptide hybrid oligomers displaying different amino acid/peptoid compositions and chain lengths was studied with respect to antimicrobial activity against Staphylococcus epidermidis both in planktonic and biofilm cultures, comparing the effects with those of the common antibiotic vancomycin. Susceptibility and time-kill assays were performed to investigate activity against planktonic cells, whilst confocal laser scanning microscopy was used to investigate the dynamics of the activity against cells within biofilms. All tested peptidomimetics were bactericidal against both exponentially growing and stationary-phase S.

Bacterial membrane activity of α-peptide/β-peptoid chimeras: influence of amino acid composition and chain length on the activity against different bacterial strains.

Background: Characterization and use of antimicrobial peptides (AMPs) requires that their mode of action is determined. The interaction of membrane-active peptides with their target is often established using model membranes, however, the actual permeabilization of live bacterial cells and subsequent killing is usually not tested. In this report, six α-peptide/β-peptoid chimeras were examined for the effect of amino acid/peptoid substitutions and chain length on the membrane perturbation and subsequent killing of food-borne and clinical bacterial isolates.

Probing the pharmacophore of ginkgolides as glycine receptor antagonists.

Ginkgolides are antagonists of the inhibitory ligand-gated ion channels for the neurotransmitters glycine and gamma-aminobutyric acid (GABA). In this study the ginkgolide structure was modified in order to investigate the minimum structural requirements for glycine receptor antagonism. The five native ginkgolides and a series of 29 ginkgolide derivatives were characterized at the three glycine receptor subtypes alpha1, alpha1beta, and alpha2, which revealed that only minor changes in the ginkgolide skeleton were allowed for maintaining glycine receptor antagonism.

Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist.

Polyamines and polyamine toxins are biologically important molecules, having modulatory effects on nucleotides and proteins. The wasp toxin, philanthotoxin-433 (PhTX-433), is a non-selective and uncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine receptors. Polyamine toxins are used for the characterization of subtypes of ionotropic glutamate receptors, the Ca2+-permeable AMPA and kainate receptors.

Stereoselective synthesis of anti-1,4-diols by a BH3.THF-mediated rearrangement of 1,2-disubstituted cyclobutenes.

A new stereoselective rearrangement of cyclobutylboranes, obtained by the hydroboration of 1,2-disubstituted cyclobutenes, provides anti-1,4-diols with good-to-excellent diastereoselectivity. The mechanism of the rearrangement is discussed based on theoretical calculations.