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41.
《Bioorganic & medicinal chemistry》2019,27(16):3546-3550
Previously we have reported on a series of pyridine-3-carboxamide inhibitors of DNA gyrase and DNA topoisomerase IV that were designed using a computational de novo design approach and which showed promising antibacterial properties. Herein we describe the synthesis of additional examples from this series aimed specifically at DNA gyrase, along with crystal structures confirming the predicted mode of binding and in vitro ADME data which describe the drug-likeness of these compounds. 相似文献
42.
以木麻黄Casuarina equisetifolia15个家系品种为材料,利用聚乙二醇6000(PEG-6000)模拟水分胁迫环境,设置三个胁迫强度处理(轻度、中度、重度胁迫),研究受胁迫2月龄木麻黄幼苗丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、脯氨酸含量的变化。结果表明,经干旱胁迫处理后,各家系幼苗叶片MDA含量随胁迫强度增大而增大,但增幅差异较大;不同干旱胁迫水平下,各家系SOD活性存在一定差异;重度胁迫条件下,除粤杂交家系外,其余家系脯氨酸含量与对照相比均为显著增加。采用主成分分析法进行抗旱性综合评价,表明MDA含量是反映水分胁迫最重要的指标。各指标综合分析结果表明,家系701、莆20、抗3、惠2、南山7和东山2抗旱性能力较好;东山短、601、59、A13抗旱能力一般;千头、粤杂交、抗1、龙4和平5抗旱能力较差。 相似文献
43.
Morán-Zorzano MT Viale AM Muñoz FJ Alonso-Casajús N Eydallín GG Zugasti B Baroja-Fernández E Pozueta-Romero J 《FEBS letters》2007,581(5):1035-1040
Escherichia coli ADP-sugar pyrophosphatase (AspP) is a "Nudix" hydrolase that catalyzes the hydrolytic breakdown of ADP-glucose linked to glycogen biosynthesis. Moderate increases of AspP activity in the cell are accompanied by significant reductions of the glycogen content. In vitro analyses showed that AspP activity is strongly enhanced by macromolecular crowding and by both glucose-1,6-bisphosphate and nucleotide-sugars, providing a first set of indicative evidences that AspP is a highly regulated enzyme. To our knowledge, AspP is the sole bacterial enzyme described to date which is activated by both G1,6P(2) and nucleotide-sugars. 相似文献
44.
To probe the size of the ion channel formed by Pseudomonas syringae lipodepsipeptide syringomycin E, we use the partial blockage of ion current by penetrating poly(ethylene glycol)s. Earlier experiments with symmetric application of these polymers yielded a radius estimate of approximately 1 nm. Now, motivated by the asymmetric non-ohmic current-voltage curves reported for this channel, we explore its structural asymmetry. We gauge this asymmetry by studying the channel conductance after one-sided addition of differently sized poly(ethylene glycol)s. We find that small polymers added to the cis-side of the membrane (the side of lipodepsipeptide addition) reduce channel conductance much less than do the same polymers added to the trans-side. We interpret our results to suggest that the water-filled pore of the channel is conical with cis- and trans-radii differing by a factor of 2-3 and that the smaller cis-radius is in the 0.25-0.35 nm range. In symmetric, two-sided addition, polymers entering the pore from the larger opening dominate blockage. 相似文献
45.
Luísa Czamanski Nora Cauã Antunes Westmann María-Eugenia Guazzaroni Chandranayaka Siddaiah Vijai Kumar Gupta Rafael Silva-Rocha 《Biotechnology advances》2019,37(8):107433
A key challenge for domesticating alternative cultivable microorganisms with biotechnological potential lies in the development of innovative technologies. Within this framework, a myriad of genetic tools has flourished, allowing the design and manipulation of complex synthetic circuits and genomes to become the general rule in many laboratories rather than the exception. More recently, with the development of novel technologies such as DNA automated synthesis/sequencing and powerful computational tools, molecular biology has entered the synthetic biology era. In the beginning, most of these technologies were established in traditional microbial models (known as chassis in the synthetic biology framework) such as Escherichia coli and Saccharomyces cerevisiae, enabling fast advances in the field and the validation of fundamental proofs of concept. However, it soon became clear that these organisms, although extremely useful for prototyping many genetic tools, were not ideal for a wide range of biotechnological tasks due to intrinsic limitations in their molecular/physiological properties. Over the last decade, researchers have been facing the great challenge of shifting from these model systems to non-conventional chassis with endogenous capacities for dealing with specific tasks. The key to address these issues includes the generation of narrow and broad host plasmid-based molecular tools and the development of novel methods for engineering genomes through homologous recombination systems, CRISPR/Cas9 and other alternative methods. Here, we address the most recent advances in plasmid-based tools for the construction of novel cell factories, including a guide for helping with “build-your-own” microbial host. 相似文献
46.
Asada H Itoh T Kodera Y Matsushima A Hiroto M Nishimura H Inada Y 《Biotechnology and bioengineering》2001,76(1):86-90
Chlorophyllide a was coupled with alpha-(3-aminopropyl)-omega-methoxypoly(oxyethylene) (PEG-NH2) to form a PEG-chlorophyllide conjugate through an acid-amide bond. The conjugate catalyzed the reduction of methylviologen in the presence of 2-mercaptoethanol. It also catalyzed the photoreduction of NADP+ or NAD+ in the presence of ascorbate as an electron donor and ferredoxin-NADP+ reductase as the coupling enzyme. Utilizing the reducing power of NADPH generated by PEG-chlorophyllide conjugate under illumination, glutamate was synthesized from 2-oxoglutarate and NH4+ in the presence of glutamate dehydrogenase. PEG-chlorophyllide conjugate was quite stable toward light illumination compared with chlorophyll a. The increase in the molecular weight of PEG in the PEG-chlorophyllide conjugates was accompanied by the enhancement of photostability of the conjugate and also by the increased solubility in the aqueous solution. 相似文献
47.
The polyethylene glycol (PEG) treatment of ciprofloxacin-Indion 234 complex was aimed to retard rapid ion exchange drug release
at gastric pH. Ciprofloxacin loading on Indion 234 was performed in a batch process, and the amount of K+ in Indion 234 displaced by drug with time was studied as equilibrium constant KDM. Drug-resin complex (DRC) was treated with aqueous PEG solution (0.5%–2% wt/vol) of different molecular weights (MWs) for
2 to 30 minutes. The PEG-treated ciprofloxacin-Indion 234 complex was evaluated for particle size, water absorption time,
and drug release at gastric pH. During drug loading on Indion 234, the equilibrium constant (KDM) increased rapidly up to 20 minutes with efficient drug loading. Increased time of immersion of the drug resinate in PEG
solutions significantly retained higher size particles upon dehydration. The larger DRC particles showed longer water absorption
times owing to compromised hydrating power. The untreated DRC showed insignificant drug release in deionized water; while
at gastric pH, ciprofloxacin release was complete in 90 minutes. A trend of increased residual particle size, proportionate
increase in water absorption time, and hence the retardation of release with time of immersion was evident in PEG-treated
DRC. The time of immersion of DRC in PEG-treated DRC. The time of immersion of DRC in PEG solution had predominant release
retardant effect, while the effect of molecular weight of PEG was insignificant. Thus, PEG treatment of DRC successfully retards
ciprofloxacin ion exchange release in acidic pH. 相似文献
48.
Hydration, structure, and molecular interactions in the headgroup region of dioleoylphosphatidylcholine bilayers: an electron spin resonance study 下载免费PDF全文
The relationship between bilayer hydration and the dynamic structure of headgroups and interbilayer water in multilamellar vesicles is investigated by electron spin resonance methods. Temperature variations of the order parameter of a headgroup spin label DPP-Tempo in DOPC in excess water and partially dehydrated (10 wt % water) show a cusp-like pattern around the main phase transition, Tc. This pattern is similar to those of temperature variations of the quadrupolar splitting of interbilayer D2O in PC and PE bilayers previously measured by 2H NMR, indicating that the ordering of the headgroup and the interbilayer water are correlated. The cusp-like pattern of these and other physical properties around Tc are suggestive of quasicritical fluctuations. Also, an increase (a decrease) in ordering of DPP-Tempo is correlated with water moving out of (into) interbilayer region into (from) the bulk water phase near the freezing point, Tf. Addition of cholesterol lowers Tf, which remains the point of increasing headgroup ordering. Using the small water-soluble spin probe 4-PT, it is shown that the ordering of interbilayer water increases with bilayer dehydration. It is suggested that increased ordering in the interbilayer region, implying a lowering of entropy, will itself lead to further dehydration of the interbilayer region until its lowered pressure resists further flow, i.e., an osmotic phenomenon. 相似文献
49.
50.
Farruggia B Nerli B Picó G 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,798(1):25-33
The theoretical framework based only on the excluded volume forces is not enough to explain the bovine serum albumin partitioning behaviour in aqueous biphasic systems. The goal of this work is to look at the phase separation via the polymer effect on the water structure. Our findings suggest that polyethyleneglycol 600-protein interaction is conducted by van der Waals forces between the hydrophobic surfaces from PEG and protein molecules, which implies the rupture of hydrogen bonds from the structured water in their neighbours. Therefore, the protein will concentrate in the most water-structured phase (polyethyleneglycol) in order to reach the minimal free energy condition. When polyethyleneglycol molecular weight increases, its exclusion from protein surface prevails, thus pushing the bovine serum albumin to the bottom phase. 相似文献