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1.
Dr. Emilianne M. Limbrick Audrey E. Yñigez-Gutierrez Callie C. Dulin Dagmara K. Derewacz Dr. Jeffrey M. Spraggins Dr. Kathryn M. McCulloch Prof. T. M. Iverson Prof. Brian O. Bachmann 《Chembiochem : a European journal of chemical biology》2020,21(23):3349-3358
Everninomicins are orthoester oligosaccharide antibiotics with potent activity against multidrug-resistant bacterial pathogens. Everninomicins act by disrupting ribosomal assembly in a distinct region in comparison to clinically prescribed drugs. We employed microporous intergeneric conjugation with Escherichia coli to manipulate Micromonospora for targeted gene-replacement studies of multiple putative methyltransferases across the octasaccharide scaffold of everninomicin effecting the A1, C, F, and H rings. Analyses of gene-replacement and genetic complementation mutants established the mutability of the everninomicin scaffold through the generation of 12 previously unreported analogues and, together with previous results, permitted assignment of the ten methyltransferases required for everninomicin biosynthesis. The in vitro activity of A1- and H-ring-modifying methyltransferases demonstrated the ability to catalyze late-stage modification of the scaffold on an A1-ring phenol and H-ring C-4’ hydroxy moiety. Together these results establish the potential of the everninomicin scaffold for modification through mutagenesis and in vitro modification of advanced biosynthetic intermediates. 相似文献
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Dawid Polak Marcin Talar Nina Wolska Dagmara W. Wojkowska Kamil Karolczak Karol Kramkowski Tomasz A. Bonda Cezary Watala Tomasz Przygodzki 《International journal of molecular sciences》2021,22(6)
Blood platelets’ adenosine receptors (AR) are considered to be a new target for the anti-platelet therapy. This idea is based on in vitro studies which show that signaling mediated by these receptors leads to a decreased platelet response to activating stimuli. In vivo evidence for the antithrombotic activity of AR agonists published to date were limited, however, to the usage of relatively high doses given in bolus. The present study was aimed at verifying if these substances used in lower doses in combination with inhibitors of P2Y12 could serve as components of dual anti-platelet therapy. We have found that a selective A2A agonist 2-hexynyl-5’-N-ethylcarboxamidoadenosine (HE-NECA) improved the anti-thrombotic properties of either cangrelor or prasugrel in the model of ferric chloride-induced experimental thrombosis in mice. Importantly, HE-NECA was effective not only when applied in bolus as other AR agonists in the up-to-date published studies, but also when given chronically. In vitro thrombus formation under flow conditions revealed that HE-NECA enhanced the ability of P2Y12 inhibitors to decrease fibrinogen content in thrombi, possibly resulting in their lower stability. Adenosine receptor agonists possess a certain hypotensive effect and an ability to increase the blood–brain barrier permeability. Therefore, the effects of anti-thrombotic doses of HE-NECA on blood pressure and the blood–brain barrier permeability in mice were tested. HE-NECA applied in bolus caused a significant hypotension in mice, but the effect was much lower when the substance was given in doses corresponding to that obtained by chronic administration. At the same time, no significant effect of HE-NECA was observed on the blood–brain barrier. We conclude that chronic administration of the A2A agonist can be considered a potential component of a dual antithrombotic therapy. However, due to the hypotensive effect of the substances, dosage and administration must be elaborated to minimize the side-effects. The total number of animals used in the experiments was 146. 相似文献
3.
Milo Hricovíni Raymond J. Owens Andrzej Bak Violetta Kozik Witold Musia Roberta Pierattelli Magdalna Mjekov Yoel Rodríguez Robert Musio Aneta Slodek Pavel tarha Karina Pitak Dagmara Sota Wioletta Florkiewicz Agnieszka Sobczak-Kupiec Josef Jampílek 《International journal of molecular sciences》2022,23(23)
The knowledge of interactions between different molecules is undoubtedly the driving force of all contemporary biomedical and biological sciences. Chemical biology/biological chemistry has become an important multidisciplinary bridge connecting the perspectives of chemistry and biology to the study of small molecules/peptidomimetics and their interactions in biological systems. Advances in structural biology research, in particular linking atomic structure to molecular properties and cellular context, are essential for the sophisticated design of new medicines that exhibit a high degree of druggability and very importantly, druglikeness. The authors of this contribution are outstanding scientists in the field who provided a brief overview of their work, which is arranged from in silico investigation through the characterization of interactions of compounds with biomolecules to bioactive materials. 相似文献
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Tomasz Kostrzewa Jakub Joczyk Joanna Drzedon Dagmara Jacewicz Magdalena Grska-Ponikowska Marcin Koaczkowski Alicja Kuban-Jankowska 《International journal of molecular sciences》2022,23(13)
One of the main goals of recent bioinorganic chemistry studies has been to design and synthesize novel substances to treat human diseases. The promising compounds are metal-based and metal ion binding components such as vanadium-based compounds. The potential anticancer action of vanadium-based compounds is one of area of investigation in this field. In this study, we present five oxovanadium(IV) and dioxovanadium(V) complexes as potential PTP1B inhibitors with anticancer activity against the MCF-7 breast cancer cell line, the triple negative MDA-MB-231 breast cancer cell line, and the human keratinocyte HaCaT cell line. We observed that all tested compounds were effective inhibitors of PTP1B, which correlates with anticancer activity. [VO(dipic)(dmbipy)]·2 H2O (Compound 4) and [VOO(dipic)](2-phepyH)·H2O (Compound 5) possessed the greatest inhibitory effect, with IC50 185.4 ± 9.8 and 167.2 ± 8.0 nM, respectively. To obtain a better understanding of the relationship between the structure of the examined compounds and their activity, we performed a computer simulation of their binding inside the active site of PTP1B. We observed a stronger binding of complexes containing dipicolinic acid with PTP1B. Based on our simulations, we suggested that the studied complexes exert their activity by stabilizing the WPD-loop in an open position and limiting access to the P-loop. 相似文献
6.
Przemysław J. Dereń Dagmara Stefańska Maciej Ptak Mirosław Mączka Wiktoria Walerczyk Grzegorz Banach 《Journal of the American Ceramic Society》2014,97(6):1883-1889
ZnAl2O4 doped with Ti4+ (2%) was synthesized by the hydrothermal method at 220°C at pressure of 25 bars. An average grain size of the as‐prepared sample was 3 nm, the samples with biggest grain size were obtained after annealing at 300°C, 500°C, 600°C, 700°C, and 900°C, diameter of the latter was about 33 nm. IR spectroscopy indicated that ZnAl2O4 was partially inverted. The degree of the inversion decreases with increase in the annealing temperature but increases with increasing Ti4+ content. Absorption and emission spectra as well as emission decay profiles were recorded at 300 and 77 K. The observed spectra are due to charge‐transfer O2??Ti4+ transitions. Color of the emission depends on the nanocrystal size and with increase in its diameter changes from violet to blue, accordingly the absorption bands exhibit redshift. The calculations based on Density Functional Theory confirmed the experimental results. 3d electrons of titanium ions form the bottom of the ZnAl2O4:Ti4+ conduction band, oxygen, aluminum or zinc vacancies create additional levels in the gahnite energy band gap. It was also found that in ZnAl2O4 aluminum or zinc vacancy induces magnetism with relatively high magnetic moment close to 1 μB per vacancy. 相似文献
7.
Dagmara Wojcik-Grzybek Magdalena Hubalewska-Mazgaj Marcin Surmiak Zbigniew Sliwowski Anna Dobrut Agata Mlodzinska Adrianna Wojcik Slawomir Kwiecien Marcin Magierowski Agnieszka Mazur-Bialy Jan Bilski Tomasz Brzozowski 《International journal of molecular sciences》2022,23(6)
Inflammatory bowel diseases (IBD) are commonly considered as Crohn’s disease and ulcerative colitis, but the possibility that the alterations in gut microbiota and oxidative stress may affect the course of experimental colitis in obese physically exercising mice treated with the intestinal alkaline phosphatase (IAP) has been little elucidated. Mice fed a high-fat-diet (HFD) or normal diet (ND) for 14 weeks were randomly assigned to exercise on spinning wheels (SW) for 7 weeks and treated with IAP followed by intrarectal administration of TNBS. The disease activity index (DAI), grip muscle strength test, oxidative stress biomarkers (MDA, SOD, GSH), DNA damage (8-OHdG), the plasma levels of cytokines IL-2, IL-6, IL-10, IL-12p70, IL-17a, TNF-α, MCP-1 and leptin were assessed, and the stool composition of the intestinal microbiota was determined by next generation sequencing (NGS). The TNBS-induced colitis was worsened in obese sedentary mice as manifested by severe colonic damage, an increase in DAI, oxidative stress biomarkers, DNA damage and decreased muscle strength. The longer running distance and weight loss was observed in mice given IAP or subjected to IAP + SW compared to sedentary ones. Less heterogeneous microbial composition was noticed in sedentary obese colitis mice and this effect disappeared in IAP + SW mice. Absence of Alistipes, lower proportion of Turicibacter, Proteobacteria and Faecalibacterium, an increase in Firmicutes and Clostridium, a decrease in oxidative stress biomarkers, 8-OHdG content and proinflammatory cytokines were observed in IAP + SW mice. IAP supplementation in combination with moderate physical activity attenuates the severity of murine colitis complicated by obesity through a mechanism involving the downregulation of the intestinal cytokine/chemokine network and oxidative stress, the modulation of the gut microbiota and an improvement of muscle strength. 相似文献
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Jan Bilski Monika Pinkas Dagmara Wojcik-Grzybek Marcin Magierowski Edyta Korbut Agnieszka Mazur-Bialy Gracjana Krzysiek-Maczka Slawomir Kwiecien Katarzyna Magierowska Tomasz Brzozowski 《International journal of molecular sciences》2022,23(7)
Both obesity and esophageal adenocarcinoma (EAC) rates have increased sharply in the United States and Western Europe in recent years. EAC is a classic example of obesity-related cancer where the risk of EAC increases with increasing body mass index. Pathologically altered visceral fat in obesity appears to play a key role in this process. Visceral obesity may promote EAC by directly affecting gastroesophageal reflux disease and Barrett’s esophagus (BE), as well as a less reflux-dependent effect, including the release of pro-inflammatory adipokines and insulin resistance. Deregulation of adipokine production, such as the shift to an increased amount of leptin relative to “protective” adiponectin, has been implicated in the pathogenesis of BE and EAC. This review discusses not only the epidemiology and pathophysiology of obesity in BE and EAC, but also molecular alterations at the level of mRNA and proteins associated with these esophageal pathologies and the potential role of adipokines and myokines in these disorders. Particular attention is given to discussing the possible crosstalk of adipokines and myokines during exercise. It is concluded that lifestyle interventions to increase regular physical activity could be helpful as a promising strategy for preventing the development of BE and EAC. 相似文献
9.
Janusz Nowicki Adam Soko?owski Dagmara Reksa 《Journal of surfactants and detergents》2011,14(2):179-184
The synthesis of new cationic carbohydrate surfactants is presented in this paper. The obtained surfactants have structures that are typical for saponins, which contain fatty amide hydrophobic chains and hydrophilic heads with cationic carbohydrate units. Their surface active properties and biodegradability have been studied. For two types, the biodegradability was above 85% and comparable to standard carbohydrate surfactants. 相似文献
10.
New Hormaphididae(Hemiptera,Aphidomorpha)from the Baltic Amber and its Palaeogeographic Significance
The present study describes a new genus and species Unicohormaphis sorini, which belongs to the subfamily Cerataphidinae. The contemporary distribution of aphids belonging to the Hormaphididae family is summarized and analyzed. According to the obtained data, the climate warming in Eocene was conducive to the expansion of the family over the areas of Europe. Subsequent climate changes, resulting from epeirogenic and orogenic movements towards the end of Eocene, led to a considerable cooling and drying of climate in the northern hemisphere. These processes contributed to the shrinking down of areas covered by subtropical forests, which constituted the habitat of Hormaphididae (Cerataphidinae). Retaining their way of life, the Cerataphidinae were forced to limit their distribution, and the representatives of the family in Europe became completely extinct. 相似文献