The synthesis of novel gramicidin S analogues having additional functionalities in the turn region by employing a biomimetic approach is described. The preservation of beta-sheet character in all analogues was established by NMR and the biological activity was evaluated.
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http://dx.doi.org/10.1016/s0968-0896(03)00219-0 | DOI Listing |
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 PDFBiochim 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 PDFJ Am Chem Soc
July 2024
Department of Chemistry, Columbia University, New York, New York 10027, United States.
Contemporary developments in the field of peptide macrocyclization methodology are imperative for enabling the advance of drug design in medicinal chemistry. This report discloses a Rh(III)-catalyzed macrocyclization via carboamidation, reacting acryloyl-peptide-dioxazolone precursors and arylboronic acids to form complex cyclic peptides with concomitant incorporation of noncanonical α-amino acids. The diverse and modular technology allows for expedient access to a wide variety of cyclic peptides from 4 to 15 amino acids in size and features simultaneous formation of unnatural phenylalanine and tyrosine derivatives with up to >20:1 diastereoselectivity.
View Article and Find Full Text PDFJ Med Chem
July 2024
School of Physics, Chemistry & Earth Sciences, The University of Adelaide, Adelaide, South Australia 5005, Australia.
Antibiotic resistance is an urgent threat to global health, with the decreasing efficacy of conventional drugs underscoring the urgency for innovative therapeutic strategies. Antimicrobial peptides present as promising alternatives to conventional antibiotics. Gramicidin S is one such naturally occurring antimicrobial peptide that is effective against , with a minimum inhibitory concentration (MIC) of 4 μg/mL (3.
View Article and Find Full Text PDFJ Am Chem Soc
June 2024
Department of Chemistry, Faculty of Natural, Mathematical, and Engineering Sciences, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.
Nonribosomal cyclic peptides (NRcPs) are structurally complex natural products and a vital pool of therapeutics, particularly antibiotics. Their structural diversity arises from the ability of the multidomain enzyme assembly lines, nonribosomal peptide synthetases (NRPSs), to utilize bespoke nonproteinogenic amino acids, modify the linear peptide during elongation, and catalyze an array of cyclization modes, e.g.
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