NMR screening of potential inhibitors of methionine γ-lyase from Citrobacter freundii

© 2014, Pleiades Publishing, Inc. Methionine γ-lyase [EC 4.4.1.11] participates in methionine catabolism in a number of bacteria and protozoa eukaryotes, including pathogenic microorganisms. The lack of this enzyme in mammals allows us consider it to be a promising target for rational antibacterial drug design. Currently, in medical practice, there are no preparations based on the inhibition of methionine γ-lyase. We present the results of a search for potential inhibitors of this enzyme using NMR screening techniques based on the identification of compounds, which are able to bind specifically to their biological target. The study included a stage of in silico virtual screening of the library of commercially available compounds and subsequent experimental selection of the leading compounds capable to interact with the enzyme. The identification of binding was carried out using saturation transfer difference (STD) spectroscopy and the WaterLOGSY technique. During the final stage, an experimental assessment of the inhibition activity of the selected compounds in the reaction of the γ elimination of L-methionine catalyzed by methionine γ-lyase was performed. Binding constants of two leading compounds were determined using the WaterLOGSY method. This study expands the structural group of potential inhibitors of methionine γ-lyase and allows us to approach the design of its inhibitors with higher efficacy

Synthesis of 2-((3-(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-4-(4-methoxyphenyl)-4-oxobut-2-enoate

Will be discussed synthesis of 2-((3-(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-4-(4-methoxyphenyl)-4-oxobut-2-enoate.The work was supported by an RFBR grant 19-43-590023

Synthesis of 2-((3-(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo [b] thiophen-2-yl)amino)-4-(4-methoxyphenyl)-4-oxobut-2-enoate

2-((3-(Ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-4-(4-methoxyphenyl)-4-oxobut-2-enoate has been synthesized by the reaction of ethyl (E)-2-((5-(4-methoxyphenyl)-2-oxofuran-3(2H)-ylidene)amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate or 2-((3-(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-4-(4-methoxyphenyl)-4-oxobut-2-enoate with potassium tert-butoxide. © 2022 Author(s).The work was done with the financial support of the Russian Foundation for Basic Research (project no. 19-43-590023)

Use of nano-sized components in multilayer composite materials

Introduction. In our country, the use of composite materials for creating parts and structural components in the construction industry is not as widespread as it could be. Composite materials are multilayer structures made of reinforcing fibers, impregnated with a polymer binder, which is also an adhesive. The strength properties of layered structural materials are achieved through various reinforcing fillers and adhesive binders. Both glass fibre and carbon fibre fabrics and fibers themselves are widely available as layered materials. Various thermosetting resins (epoxy, phenolic, polyester, polyimide, polyamideimide, polyamide, etc.) are used as binding components. Among them, epoxy resins with high strength, wettability and adhesion to various materials are widely used. Layered composite materials (LCM) are used to make polymer reinforcement for reinforcing concrete structures, various pipes, shell frames to strengthen existing metal and reinforced concrete structures, load-bearing elements in light-loaded structures of bridges and crossings. However, at the same time they have a significant drawback – low interlayer strength (propensity to layering). As a result, the connection between the layers is disrupted, which leads to a significant decrease in the rigidity and strength of the structure. This phenomenon applies to all types of fabrics and fibers. Most often, defects in the form of layering are formed under the influence of shock loads. To improve the performance characteristics of such materials, various fillers have now begun to be used – powders (micro- and nano-sized) introduced into binder compositions. Main part. The analysis of the academic literature has shown that it is possible to increase the interlayer strength in structural elements made of LCM through the use of nanofilled binders and the introduction of nanoadditives into the interlayer space of layered materials. The article reviews the related inventions in Russia, USA, etc., which can be applied in the construction industry using nanodispersed components. With the widespread use of the presented materials (in bridges, pedestrian bridges and bridge decks, etc.), significant performance advantages can be achieved compared to materials traditionally used in the construction industry. Methods and materials. By comparing the data from the submitted patents for inventions, it was revealed that the introduction of from 2% to 5% of various nanocomponents to form a nanocomposite material provides a new means of modifying the physical properties of polymer binders. Results. It was revealed that the use of nanoparticles ensures the decrease in the fluidity of prepregs and the gelation time, and the increase in residual compressive strength and specific fracture energy – indicators characterizing the crack resistance of composite materials. As a result, fracture toughness, endurance and survivability increase. Conclusion. Increasing the reliability of composite materials leads to longer service life of products and structural elements in the construction industr

Organizational evolution and the Olympic Games: the case of sport climbing

This paper discusses the processes underpinning the evolutionary development of sport climbing in recent decades, with a particular focus on the impact of its inclusion in the Olympic Games. New institutionalism and resource-dependence theory provide an analytical and explanatory framework for this study. The research adopted a qualitative method strategy comprising a series of interviews and the analysis of documents, reports, press and social media. The recent inclusion of the sport in the Tokyo 2020 Olympic programme has created challenges, primarily because of strong values inherent within the sport. The research, however, shows that the values of a sport can expand and develop in order to fit the regulatory legitimacy required by inclusion in the Olympic Games. Nonetheless, the research also shows that involvement with the IOC raises questions about who ‘owns’ the sport