Structure-Based Design of an RNase Chimera for Antimicrobial Therapy

Bacterial resistance to antibiotics urges the development of alternative therapies. Based on the structure-function of antimicrobial members of the RNase A superfamily, we have developed a hybrid enzyme. Within this family, RNase 1 exhibits the highest catalytic activity and the lowest cytotoxicity; in contrast, RNase 3 shows the highest bactericidal action, alas with a reduced catalytic activity. Starting from both parental proteins, we designed a first RNase 3/1-v1 chimera. The construct had a catalytic activity much higher than RNase 3, unfortunately without reaching an equivalent antimicrobial activity. Thus, two new versions were created with improved antimicrobial properties. Both of these versions (RNase 3/1-v2 and -v3) incorporated an antimicrobial loop characteristic of RNase 3, while a flexible RNase 1-specific loop was removed in the latest construct. RNase 3/1-v3 acquired both higher antimicrobial and catalytic activities than previous versions, while retaining the structural determinants for interaction with the RNase inhibitor and displaying non-significant cytotoxicity. Following, we tested the constructs’ ability to eradicate macrophage intracellular infection and observed an enhanced ability in both RNase 3/1-v2 and v3. Interestingly, the inhibition of intracellular infection correlates with the variants’ capacity to induce autophagy. We propose RNase 3/1-v3 chimera as a promising lead for applied therapeutics.

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Magnetite Nanoparticles Functionalized with RNases against Intracellular Infection of Pseudomonas aeruginosa

Pharmaceutics ◽

10.3390/pharmaceutics12070631 ◽

2020 ◽

Vol 12 (7) ◽

pp. 631

Author(s):

Nathaly Rangel-Muñoz ◽

Alejandra Suarez-Arnedo ◽

Raúl Anguita ◽

Guillem Prats-Ejarque ◽

Johann F. Osma ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Activity ◽

Magnetite Nanoparticles ◽

Bacterial Infections ◽

Cell Damage ◽

Resistance Mechanisms ◽

Rnase A ◽

Hybrid Protein ◽

Intracellular Infection ◽

Rnase A Superfamily

Current treatments against bacterial infections have severe limitations, mainly due to the emergence of resistance to conventional antibiotics. In the specific case of Pseudomonas aeruginosa strains, they have shown a number of resistance mechanisms to counter most antibiotics. Human secretory RNases from the RNase A superfamily are proteins involved in a wide variety of biological functions, including antimicrobial activity. The objective of this work was to explore the intracellular antimicrobial action of an RNase 3/1 hybrid protein that combines RNase 1 high catalytic and RNase 3 bactericidal activities. To achieve this, we immobilized the RNase 3/1 hybrid on Polyetheramine (PEA)-modified magnetite nanoparticles (MNPs). The obtained nanobioconjugates were tested in macrophage-derived THP-1 cells infected with Pseudomonas aeruginosa PAO1. The obtained results show high antimicrobial activity of the functionalized hybrid protein (MNP-RNase 3/1) against the intracellular growth of P. aeruginosa of the functionalized hybrid protein. Moreover, the immobilization of RNase 3/1 enhances its antimicrobial and cell-penetrating activities without generating any significant cell damage. Considering the observed antibacterial activity, the immobilization of the RNase A superfamily and derived proteins represents an innovative approach for the development of new strategies using nanoparticles to deliver antimicrobials that counteract P. aeruginosa intracellular infection.

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Development of palladium catalysts modified by ruthenium and molybdenum as anode in direct ethanol fuel cell

Materials for Renewable and Sustainable Energy ◽

10.1007/s40243-020-00187-1 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Yonis Fornazier Filho ◽

Ana Caroliny Carvalho da Cruz ◽

Rolando Pedicini ◽

José Ricardo Cezar Salgado ◽

Priscilla Paiva Luz ◽

...

Keyword(s):

Catalytic Activity ◽

Palladium Catalysts ◽

Carbon Support ◽

X Ray Diffraction ◽

Direct Ethanol Fuel Cell ◽

Pd Catalysts ◽

Bifunctional Mechanism ◽

Catalytic Activities ◽

Intrinsic Mechanism ◽

Ternary Catalysts

AbstractPhysical and electrochemical properties of Pd catalysts combined with Ru and Mo on carbon support were investigated. To this end, Pd, Pd1.3Ru1.0, Pd3.2Ru1.3Mo1.0 and Pd1.5Ru0.8Mo1.0 were synthesized on Carbon Vulcan XC72 support by the method of thermal decomposition of polymeric precursors and then physically and electrochemically characterized. The highest reaction yields are obtained for Pd3.2Ru1.3Mo1.0/C and Pd1.5Ru0.8Mo1.0/C and, as demonstrated by thermal analysis, they also show the smallest metal/carbon ratio compared the other catalysts. XRD (X-ray Diffraction) and Raman analyses show the presence of PdO and RuO2 for the Pd/C and the Pd1.3Ru1.0/C catalysts, respectively, a fact not observed for the Pd3.2Ru1.3 Mo1.0 /C and the Pd1.5Ru0.8Mo1.0/C catalysts. The catalytic activities were tested for the ethanol oxidation in alkaline medium. Cyclic voltammetry (CV) shows Pd1.3Ru1.0/C exhibiting the highest peak of current density, followed by Pd3.2Ru1.3Mo1.0/C, Pd1.5Ru0.8Mo1.0/C and Pd/C. From, chronoamperometry (CA), it is possible to observe the lowest rate of poisoning for the Pd1.3Ru1.0/C, followed by Pd3.2Ru1.3Mo1.0/C, Pd1.5Ru0.8Mo1.0/C and Pd/C. These results suggested that catalytic activity of the binary and the ternary catalysts are improved in comparison with Pd/C. The presence of RuO2 activated the bifunctional mechanism and improved the catalytic activity in the Pd1.3Ru1.0/C catalyst. The addition of Mo in the catalysts enhanced the catalytic activity by the intrinsic mechanism, suggesting a synergistic effect between metals. In summary, we suggest that it is possible to synthesize ternary PdRuMo catalysts supported on Carbon Vulcan XC72, resulting in materials with lower poisoning rates and lower costs than Pd/C. Graphic abstract

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Active Pd(ii) complexes: enhancing catalytic activity by ligand effect for carbonylation of methyl nitrite to dimethyl carbonate

Catalysis Science & Technology ◽

10.1039/c7cy01305a ◽

2017 ◽

Vol 7 (17) ◽

pp. 3785-3790 ◽

Cited By ~ 10

Author(s):

Hong-Zi Tan ◽

Zhi-Qiao Wang ◽

Zhong-Ning Xu ◽

Jing Sun ◽

Zhe-Ning Chen ◽

...

Keyword(s):

Catalytic Activity ◽

Dimethyl Carbonate ◽

Ligand Effect ◽

Methyl Nitrite ◽

Catalytic Activities

The catalytic activities of Pd(ii) complexes for carbonylation of methyl nitrite to dimethyl carbonate could be enhanced by ligand effect.

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A graphdiyne-based carbon material for electroless deposition and stabilization of sub-nanometric Pd catalysts with extremely high catalytic activity

Journal of Materials Chemistry A ◽

10.1039/c9ta03621k ◽

2019 ◽

Vol 7 (21) ◽

pp. 13142-13148 ◽

Cited By ~ 12

Author(s):

Liang-Liang Yang ◽

Hong-Juan Wang ◽

Juan Wang ◽

Yu Li ◽

Wen Zhang ◽

...

Keyword(s):

Catalytic Activity ◽

Carbon Material ◽

Electroless Deposition ◽

Suzuki Coupling ◽

High Catalytic Activity ◽

Coupling Reactions ◽

Pd Catalysts ◽

Catalytic Activities

A new graphdiyne-based carbon material was synthesized as an ideal substrate for electroless deposition and stabilization of sub-nanometric Pd catalysts, which showed extremely high catalytic activities for the reduction of nitroarenes and Suzuki coupling reactions.

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Synthesis of concave gold nanocuboids with high-index facets and their enhanced catalytic activity

Chemical Communications ◽

10.1039/c5cc02106e ◽

2015 ◽

Vol 51 (58) ◽

pp. 11591-11594 ◽

Cited By ~ 18

Author(s):

Lidong Li ◽

Yi Peng ◽

Yonghai Yue ◽

Ye Hu ◽

Xiu Liang ◽

...

Keyword(s):

Catalytic Activity ◽

High Index ◽

Catalytic Activities ◽

Growth Method ◽

Seed Mediated

Novel concave gold nanocuboids bounded by 24 high-index {611} facets are synthesized using the seed-mediated growth method via an overgrowth mechanism, which exhibit excellent catalytic activities over certain reactions.

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In Vitro Hepatic Assessment of Cineole and Its Derivatives in Common Brushtail Possums (Trichosurus vulpecula) and Rodents

Biology ◽

10.3390/biology10121326 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1326

Author(s):

Ravneel R. Chand ◽

Mhairi Nimick ◽

Belinda Cridge ◽

Rhonda J. Rosengren

Keyword(s):

Catalytic Activity ◽

Management Strategies ◽

Brushtail Possum ◽

Trichosurus Vulpecula ◽

Cytochrome P450 3A ◽

Phascolarctos Cinereus ◽

Catalytic Activities ◽

Rats And Mice ◽

Drug Metabolising Enzymes

Folivore marsupials, such as brushtail possum (Trichosurus Vulpecula) and koala (Phascolarctos cinereus), can metabolise higher levels of dietary terpenes, such as cineole, that are toxic to eutherian mammals. While the highly efficient drug metabolising enzymes, cytochrome P450 3A (CYP3A) and phase II conjugating enzymes (UDP-glucuronosyltransferase, UGT), are involved in the metabolism of high levels of dietary terpenes, evidence for inhibitory actions on these enzymes by these terpenes is scant. Thus, this study investigated the effect of cineole and its derivatives on catalytic activities of hepatic CYP3A and UGT in mice, rats, and possums. Results showed that cineole (up to 50 µM) and its derivatives (up to 25 µM) did not significantly inhibit CYP3A and UGT activities in mice, rats, and possums (both in silico and in vitro). Interestingly, basal hepatic CYP3A catalytic activity in the possums was ~20% lower than that in rats and mice. In contrast, possums had ~2-fold higher UGT catalytic activity when compared to mice and rats. Thus, these basal enzymatic differences may be further exploited in future pest management strategies.

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ANTIBACTERIAL ACTIVITY OF THE ETHANOL EXTRACT OF Eugenia dysenterica DC (MYRTACEAE)

Periódico Tchê Química ◽

10.52571/ptq.v16.n32.2019.275_periodico32_pgs_257_262.pdf ◽

2019 ◽

Vol 16 (32) ◽

pp. 257-262

Author(s):

Thaís Paula Rodrigues GONÇALVES ◽

William Gustavo LIMA ◽

Izabela Caputo Assis SILVA ◽

Adriano Guimarães PARREIRA ◽

Luciana Alves Rodrigues dos Santos LIMA

Keyword(s):

Bacterial Resistance ◽

Ethanol Extract ◽

New Drugs ◽

Bactericidal Action ◽

Phytochemical Screening ◽

Biological Potential ◽

Important Field ◽

Phytochemical Profile ◽

Eugenia Dysenterica ◽

Antibacterial Potential

The large variety of plant specimens found in Brazil with still unexplored medicinal potential, combined with the increase in bacterial resistance to antimicrobials traditionally employed, opens an important field of research aimed at prospecting new drugs. In this context the objective of this work was to evaluate the antibacterial potential of Eugenia dysenterica and to characterize its phytochemical profile. Ethanolic extracts were obtained by drying, grinding, turbo-extraction and lyophilization of the leaves of the plant. The CIM and CBM tests were performed to evaluate the antimicrobial potential on the following strains: Proteus mirabilis ATCC 15290, Echerichia coli ATCC25922, Staphylococcus aureus ATCC29213 and Staphylococcus epidermides ATCC 12228. E. dysenterica presented bactericidal action at 2mg.ml-1 against S. aureus and bacteriostatic at 1mg.ml-1 against P. mirabilis. Several phenolic compounds were detected in the phytochemical screening, and the presence of these compounds may justify the biological potential of this plant.

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Bi-metallic MOF-919 (Fe-Cu) nanozyme capable of bifunctional enzyme-mimicking catalytic activity

Chemical Communications ◽

10.1039/d1cc05908d ◽

2021 ◽

Author(s):

Sivasankar Kulandaivel ◽

Chia-Her Lin ◽

Yi-Chun Yeh

Keyword(s):

Catalytic Activity ◽

Metal Organic Framework ◽

Bifunctional Enzyme ◽

Catalytic Activities ◽

Enzyme Mimicking ◽

Metal Organic ◽

Organic Framework

In this study, we report on a bi-metal organic framework MOF-919 (Fe-Cu) capable of bifunctional-enzyme mimicking activity with oxidase- and peroxidase-like activities. The catalytic activities were examined by using o-phenylenediamine...

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