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1.
Colloids Surf B Biointerfaces ; 213: 112425, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35231687

RESUMEN

Antibiotics, being critical antimicrobial agents, have been widely used for treating bacterial infections. However, prolonged use of antibiotics can induce drug resistance resulting in "superbug" that threatens human health. Therefore, developing antibiotic-free materials with intrinsic antibacterial properties is the key to the "superbug" challenge. In this study, two highly efficient metal-organic frameworks (MOFs) were successfully assembled through synergistic use of the antibacterial properties of reactive organic radicals and silver (Ag) cations. These hybrid Ag-based materials possessed radical-doped characteristics, continuously releasing Ag+, which significantly inhibited the growth of four common Gram-negative and Gram-positive human pathogens (Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus), and particularly two multi-drug-resistance bacteria (MRSA and MDR-PA). Furthermore, in vivo assays indicated that the synergistic antibacterial effect of these compounds could significantly accelerate the healing rate of infected wounds in mice. Blood biochemistry and histological analyses of main organs in treated mice also exhibited negligible cytotoxicity. This study unveiled the promising potential of Ag-MOFs for anti-infective therapies and future clinical applications.


Asunto(s)
Nanopartículas del Metal , Estructuras Metalorgánicas , Infecciones Estafilocócicas , Animales , Antibacterianos/química , Antibacterianos/farmacología , Escherichia coli , Nanopartículas del Metal/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Ratones , Pruebas de Sensibilidad Microbiana , Plata/química , Plata/farmacología , Staphylococcus aureus
2.
Chem Commun (Camb) ; 56(92): 14353-14356, 2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33169746

RESUMEN

In the present work, we have introduced a series of stable radical-doped coordination compounds composed of donor-acceptor structures and shown to produce organic radicals in situ as a result of unconventional lone pair-π interactions in ambient conditions. Inconspicuous lone pair-π and C-Hπ interactions were shown to play a key role in self-assembly as well as the charge transfer process, resulting in a long-lived charge-separated state able to generate organic radicals. The resultant species displayed broad-spectrum antimicrobial activity, including against multi-drug-resistant bacteria. This study unveiled the promise of reactive organic radical-doped materials as a new platform for developing antimicrobial agents that can overcome antibiotic resistance.


Asunto(s)
Antibacterianos/química , Radicales Libres/química , Estructuras Metalorgánicas/química , Naftalimidas/química , Antibacterianos/farmacología , Bacillus subtilis , Farmacorresistencia Bacteriana Múltiple , Escherichia coli , Estructuras Metalorgánicas/farmacología , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa , Semiconductores , Staphylococcus aureus , Relación Estructura-Actividad
3.
Biochem Biophys Res Commun ; 533(4): 1115-1121, 2020 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-33036755

RESUMEN

Inorganic pyrophosphatase (PPase) plays an essential role in energy conservation and provides energy for many biosynthetic pathways. Here, we present two three-dimensional structures of PPase from Homo sapiens (Hu-PPase) at 2.38 Å and 3.40 Å in different crystallization conditions. One of the Hu-PPase structures complex of two magnesium metal ions was determined to be a monomer (Hu-PPase-mono) here, while the other one to be a dimer-dimer (Hu-PPase-dd). In each asymmetric unit of Hu-PPase-mono, there are four α-helices and ten ß-strands and folds as a barrel structure, and the active site contains two magnesium ions. Like PPases from many species, we found that Hu-PPase was able to undergo self-assembly. To our surprise, disruption of the self-assembly of Hu-PPase did not influence its enzymatic activity or the ability to promote cell growth. Our work uncovered that different structure forms of Hu-PPase and found that the pyrophosphatase activity of Hu-PPase is independent of its self-assembly.


Asunto(s)
Proliferación Celular/genética , Pirofosfatasa Inorgánica/química , Pirofosfatasa Inorgánica/metabolismo , Magnesio/química , Secuencia de Aminoácidos , Sitios de Unión , Catálisis , Cristalografía por Rayos X , Dimerización , Células HEK293 , Células HeLa , Humanos , Pirofosfatasa Inorgánica/genética , Modelos Moleculares , Conformación Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Proteínas Recombinantes
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