Li JG
Mechanism of Polyamine Induced Colistin Resistance through Electrostatic Networks on Bacterial Outer Membranes
Naturally occurring linear polyamines are known to enable bacteria to be resistant to cationic membrane active peptides. To understand this protective mechanism, molecular dynamics simulations are employed to probe their effect on a model bacterial outer membrane.
ReadReactive Metabolite-induced Protein Glutathionylation: a Potentially Novel Mechanism Underlying Acetaminophen Hepatotoxicity
Although covalent protein binding is established as the pivotal event underpinning acetaminophen (APAP) toxicity, its mechanistic details remain unclear. In this study, we demonstrated that APAP induces widespread protein glutathionylation in a time-, dose- and bioactivation-dependent manner in HepaRG cells.
ReadAntimicrobial activity profiles of Amphiphilic Xanthone derivatives are a function of their molecular Oligomerization
Currently, membrane-targeting small antimicrobial peptidomimetics (SAP) are important in antibiotic development because bacteria appear to develop resistance to these surface-active compounds less readily. However, the molecular membrane-targeting action of SAPs has received little attention. In this study, we investigated the effect of oligomerization of amphiphilic xanthone, a model SAP, on its antimicrobial properties against both Gram-positive and Gram-negative bacteria.
ReadElucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH2
Linear antimicrobial peptides, with their rapid bactericidal mode of action, are well-suited for development as topical antibacterial drugs. We recently designed a synthetic linear 4-residue peptide, BRBR-NH2, with potent bactericidal activity against Staphylococcus aureus (MIC 6.25 μM), the main causative pathogen of human skin infections with an unknown mechanism of action.
ReadThe effect of molecular shape on oligomerization of hydrophobic drugs: molecular simulations of ciprofloxacin and Nutlin
Molecular aggregation plays a significant role in modulating the solubility, permeability, and bioactivity of drugs. The propensity to aggregate depends on hydrophobicity and on molecular shape. Molecular dynamics simulations coupled with enhanced sampling methods are used to explore the early stages of oligomerization of two drug molecules which have a strong aggregation propensity, but with contrasting molecule shapes: the antibiotic ciprofloxacin and the anticancer drug Nutlin-3A.
ReadMolecular insights into the membrane affinities of model hydrophobes
embrane-active antibiotics are of great interest in fighting bacterial resistance. α-Mangostin is a membrane-active molecule, but there are no details of its mechanism of action at the atomistic level.
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