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981.
982.
All cells must manage deficiency, sufficiency, and excess of essential metal ions. Although iron has been one of most important metals in biology for billions of years, the mechanisms by which bacteria cope with high intracellular iron concentrations are only recently coming into focus. Recent work has suggested that an RNA riboswitch (czcD or “NiCo”), originally thought to respond specifically to CoII and NiII excess, is more likely a selective regulator of FeII levels in important human gut bacteria and pathogens. We discuss the challenges and controversies encountered in the characterization of iron-responsive riboswitches, and we suggest a physiological role in responding to iron overload, perhaps during anaerobiosis. Finally, we place these riboswitches in the context of the better understood mechanisms of protein-based metal ion regulation, proposing that riboswitch-mediated mechanisms may be particularly important in regulating transport of the weakest-binding biological divalent metal ions, MgII, MnII, and FeII. 相似文献
983.
Inorganic metals supplement the chemical repertoire of organic molecules, especially proteins. This requires the correct metals to associate with proteins at metalation. Protein mismetalation typically occurs when excesses of unbound metals compete for a binding site ex vivo. However, in biology, excesses of metal-binding sites typically compete for limiting amounts of exchangeable metals. Here, we summarise mechanisms of metal homeostasis that sustain optimal metal availabilities in biology. We describe recent progress to understand metalation by comparing the strength of metal binding to a protein versus the strength of binding to competing sites inside cells. 相似文献
984.
香豆素类化合物是自然界中一类重要的化合物,具有抗肿瘤、抗凝血、抗菌、杀虫等多种生物活性,应用领域广泛。目前大多数香豆素类化合物从植物中提取,受环境因素影响较大,得率低、成本高,不利于大规模生产,从而限制了其应用和推广。利用合成生物学的思路合成香豆素类化合物具有无污染、原料易得、成本低、过程可控等优势。对香豆素类化合物生物合成途径的研究,尤其是靶标天然产物生物合成表达元件、宿主和发酵条件的优化,以及合成途径中关键酶的挖掘,已经成为研究热点。综述香豆素类化合物及其衍生物的结构、功能和生物合成研究进展,为其生物合成路径中的基因挖掘及异源表达提供参考。 相似文献
985.
本文通过对HEMWat溶剂体系中28种常用溶剂系统单相以及整体极性进行系统分析,探讨了无法用常规J型逆流色谱实现对大极性化合物实现有效分离的原因。根据分析结果建立了一种以分离物质理化性质为基础选择潜在改性剂,样品在溶剂系统上相中的溶解程度为判断指标进行筛选逆流色谱溶剂系统改性剂,进而得到适宜的溶剂系统对大极性海参多肽样品进行系统分段方法。经过两步分离,共得到8个随极性分布的海参多肽片段,为海参多肽最佳活性物质的追踪和筛选提供了技术支持。 相似文献
986.
Naiade B.G. Marques Raquel G. Jacob Gelson Perin Eder J. Lenardo Diego Alves Mrcio S. Silva 《Chirality》2019,31(1):41-51
Here, we report the general strategies by which NMR spectroscopy can be used to determine the enantiopurity and absolute configuration of chalcogen containing secondary alcohols, including the evaluation of the use of chiral solvating and chiral derivatizing agents. The BINOL/DMAP ternary complex demonstrated a simple and fast protocol for determining enantiopurity. The drug Naproxen afforded a stable, nonhygroscopic, and readily available chiral derivatizing agent (CDA) for NMR chiral discrimination of chalcogen containing secondary alcohols. The chiral recognition by CDA and chiral solvating agent (CSA) was assessed using 1H, 77Se‐{1H}, and 125Te‐{1H} NMR spectroscopy. A simple model for the assignment of the absolute configuration from NMR data is presented. 相似文献
987.
《Bioorganic & medicinal chemistry》2019,27(12):2537-2545
Protease roles in cancer progression have been demonstrated and their inhibitors display antitumor effects. Cathepsins are lysosomal cysteine proteases that have increased expression in tumor cells, and tellurium compounds were described as potent cysteine protease inhibitors and also assayed in several animal models. In this work, the two enantiomeric forms of 1-[Butyl(dichloro)-λ4-tellanyl]-2-[1S-methoxyethyl]benzene (organotelluranes RF-13R and RF-13S) were evaluated as inhibitors of cathepsins B and L, showing significant enantiodiscrimination. We observed their cytotoxic effects on a murine melanoma model, effectively inhibiting tumor progression in vivo. The enantiomers were able to inhibit melanoma cell viability, migration and invasion in vitro. Besides, RF-13S and RF-13R were able to inhibit endothelial cell angiogenesis using a tube formation assay in vitro, in a stereodependent manner. These organotelluranes affected cell morphology, showing disassembling of the actin cytoskeleton. These results suggest organotelluranes as potential antitumor agents, acting directly on tumor cell proliferation, migration and invasion, and on endothelial cells, disrupting angiogenesis, showing low toxicity and high efficiency. Taken together our results suggest that this class of compounds should be further studied to reveal their potential as antitumoral agents. 相似文献
988.
989.
《Bioorganic & medicinal chemistry letters》2019,29(16):2197-2202
The binding of ten quinoxaline compounds (1–10) to a site adjacent to S2 (AS2) of cruzain (CRZ) was evaluated by a protocol that include a first analysis through docking experiments followed by a second analysis using the Molecular Mechanics-Poisson-Boltzmann Surface Area method (MM-PBSA). Through them we demonstrated that quinoxaline compounds bearing substituents of different sizes at positions 3 or 4 of the heterocyclic ring might interact with the AS2, particularly interesting site for drug design. These compounds showed docking scores (ΔGdock) which were similar to those estimated for inhibitors that bind to the enzyme through non-covalent interactions. Nevertheless, the free binding energies (ΔG) values estimated by MM-PBSA indicated that the derivatives 8–10, which bear bulky substituents at position 3 of the heterocycle ring, became detached from the binding site under a dynamic study. Surprisingly, the evaluation of the inhibitory activity of cruzipain (CZ) of some derivatives showed that they increase the enzymatic activity. These results lead us to conclude about the relevance of AS2 as a pocket for compounds binding site, but not necessarily for the design of anti-chagasic compounds. 相似文献
990.
AbstractFour organic solvents along with water were applied for the conventional extraction of Eucalyptus camaldulensis (Myrtaceae), phenolic contents and antioxidant activities were investigated through variable protocols and correlation coefficients were considered, the phenolic composition was also characterized by Gas chromatography-mass spectrometry (GC-MS). Using solvents with dissimilar polarities affected the phenolic yields extracted from E. camaldulensis and their related antioxidant activities varied significantly among the four investigated plant organs. The leaf extract of acetone 70% contained the highest amount of phenolic compounds (46.56?mg/g dry weight); while the bud-water boiled extract maintained the maximum value of tannins (45.68?mg/g dry weight). Correlation coefficients indicated that phenolic compounds were mostly accountable for the phosphomolybednum antioxidant potentials (0.520), followed by tannins (0.460). Also, both the reducing power activities and hydrogen peroxide scavenging of E. camaldulensis extracts positively correlated with tannins, but at different significance degrees. However, the GC-MS analysis revealed that most of the detected phenolic constituents were more abundant in the plant seed. So, the existence of some other compounds such as organic acids, along with phenolics, may have increased the antioxidant potentials of leaf and bud. Undeniably, the optimization of extraction conditions could stimulate the antioxidant capabilities of the plant extracts of E. camaldulensis. 相似文献