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Expanding the therapeutic window of gramicidin S towards a safe and effective systemic treatment of methicillin-resistant S. aureus infections.
Eur J Med Chem
February 2025
Department of Chemistry, School of Physics, Chemistry and Earth Sciences, The University of Adelaide, Adelaide, South Australia, 5005, Australia. Electronic address:
The rise of multidrug-resistant bacteria, such as Methicillin-resistant Staphylococcus aureus (MRSA), necessitates the development of new antibacterial therapies. Antimicrobial peptides offer a promising alternative to conventional antibiotics due to their unique mechanisms of action. Gramicidin S exhibits potent bactericidal activity against S.
View Article and Find Full Text PDFPuckering effects of 4-hy-droxy-l-proline isomers on the conformation of ornithine-free Gramicidin S.
Acta Crystallogr E Crystallogr Commun
September 2024
Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 590-1094, Japan.
The cyclic peptide (Val-Leu-Leu-d-Phe-Pro) (peptide ) was specifically designed for structural chemistry investigations, drawing inspiration from Gramicidin S (GS). Previous studies have shown that Pro residues within adopt a down-puckering conformation of the pyrrolidine ring. By incorporating fluoride-Pro with 4-/-isomers into , an up-puckering conformation was successfully induced.
View Article and Find Full Text PDFModifying Membranotropic Action of Antimicrobial Peptide Gramicidin S by Star-like Polyacrylamide and Lipid Composition of Nanocontainers.
Int J Mol Sci
August 2024
Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy.
Gramicidin S (GS), one of the first discovered antimicrobial peptides, still shows strong antibiotic activity after decades of clinical use, with no evidence of resistance. The relatively high hemolytic activity and narrow therapeutic window of GS limit its use in topical applications. Encapsulation and targeted delivery may be the way to develop the internal administration of this drug.
View Article and Find Full Text PDFMitochondrial uncoupling caused by a wide variety of protonophores is differently sensitive to carboxyatractyloside in rat heart and liver mitochondria.
Biochim Biophys Acta Bioenerg
November 2024
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. Electronic address:
Mitochondrial uncoupling by small-molecule protonophores is generally accepted to proceed via transmembrane proton shuttling. The idea of facilitating this process by the adenine nucleotide translocase ANT originated primarily from the partial reversal of the DNP-induced mitochondrial uncoupling by the ANT inhibitor carboxyatractyloside (CATR). Recently, the sensitivity to CATR was also observed for the action of such potent OxPhos uncouplers as BAM15, SF6847, FCCP and niclosamide.
View Article and Find Full Text PDFThe microbiome-derived antibacterial lugdunin acts as a cation ionophore in synergy with host peptides.
mBio
September 2024
Interfaculty Institute of Microbiology and Infection Medicine, Microbial Bioactive Compounds, University of Tübingen, Tübingen, Germany.
Unlabelled: Lugdunin is a microbiome-derived antibacterial agent with good activity against Gram-positive pathogens and in animal models of nose colonization and skin infection. We have previously shown that lugdunin depletes bacterial energy resources by dissipating the membrane potential of . Here, we explored the mechanism of action of lugdunin in more detail and show that lugdunin quickly depolarizes cytoplasmic membranes of different bacterial species and acidifies the cytoplasm of within minutes due to protonophore activity.
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