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141.
Alexander J. Bridges Arthur Lee C.Eric Schwartz Murray J. Towle Bruce A. Littlefield 《Bioorganic & medicinal chemistry》1993,1(6):403-410
Efficient syntheses of structurally novel 4-substituted benzo[b]thiophene-2-carboxamidmes 1–3, which selectively inhibit urokinase-type plasminogen activator (uPA) with IC50 values of 70–320 nM, are described. The key intermediate, methyl 4-iodobenzo[b]thiophene-2-carboxylate (7), is prepared from 3-fluoroiodobenzene in two steps in 70% overall yield via fluorine-directed metalation/formylation and subsequent thiophene annulation. Amidination of ester 7 gives the 320 nM inhibitor 1. Palladium-catalyzed arylacetylene and vinyl stannane couplings with ester 7 or 4-iodobenzo[b]thiophene-2-carbonitrile (16, derived from 7), respectively, followed by amidination leads to the more potent inhibitors 2 (IC50 = 133 nM) and 3 (IC50 = 70 nM). These compounds represent an important new class of synthetic uPA inhibitors, with carboxamidine 3 being the most potent selective inhibitor currently described in the literature. 相似文献
142.
R. Ashton Lavoie Jeffrey T. Zugates Andrew T. Cheeseman Matt A. Teten Srivatsan Ramesh Julia M. Freeman Summer Swango Jeremy Fitzpatrick Amod Joshi Bradley Hollers Zufan Debebe Tyler K. Lindgren Amber N. Kozak Vinay K. Kondeti Mary K. Bright Eric J. Yearley Alexander Tracy Jacob A. Irwin Michael Guerrero 《Biotechnology and bioengineering》2023,120(10):2953-2968
Adeno-associated virus-based gene therapies have demonstrated substantial therapeutic benefit for the treatment of genetic disorders. In manufacturing processes, viral capsids are produced with and without the encapsidated gene of interest. Capsids devoid of the gene of interest, or “empty” capsids, represent a product-related impurity. As a result, a robust and scalable method to enrich full capsids is crucial to provide patients with as much potentially active product as possible. Anion exchange chromatography has emerged as a highly utilized method for full capsid enrichment across many serotypes due to its ease of use, robustness, and scalability. However, achieving sufficient resolution between the full and empty capsids is not trivial. In this work, anion exchange chromatography was used to achieve empty and full capsid resolution for adeno-associated virus serotype 5. A salt gradient screen of multiple salts with varied valency and Hofmeister series properties was performed to determine optimal peak resolution and aggregate reduction. Dual salt effects were evaluated on the same product and process attributes to identify any synergies with the use of mixed ion gradients. The modified process provided as high as ≥75% AAV5 full capsids (≥3-fold enrichment based on the percent full in the feed stream) with near baseline separation of empty capsids and achieved an overall vector genome step yield of >65%. 相似文献
143.
Galls produced by the cecidomynd Lastoptera ephedncola on Ephedia trifurca always have a black ring associated with them while galls produced by the congener L ephedrae never do Black ring material after microscopic examination and culture proved to be Aureobasidium pullulans In addition to lacking black ring material neither L ephedrae galls nor healthy stems consistently yielded Aureobasidium on culture Gall and larva size measurements indicated that continued larval presence is not necessary for gall development, suggesting fungus initiated gall formation However inoculation of healthy stems with Aureobasidium caused lesions hut not galls The mycelium m galls did not appear grazed and neither larvae nor pupae contained Aureobasidium propagules suggesting that larvae do not feed directly on fungi These data also suggest that there is no trans-pupal passage of fungus from larvae or pupae to adults Newly emerged females do not carry fungal propagules suggesting that thcy are not inoculated upon exiting the gall Gall position leaf culture and stem culture data suggest that the fungus is picked up from leaves prior to oviposition 相似文献
144.
Anita Shepherd Danny Awty-Carroll Jason Kam Chris Ashman Elena Magenau Enrico Martani Mislav Kontek Andrea Ferrarini Stefano Amaducci Chris Davey Vanja Jurišić Gert-Jan Petrie Mohamad Al Hassan Isabelle Lamy Iris Lewandowski Emmanuel de Maupeou Jon McCalmont Luisa Trindade Kasper van der Cruijsen Philip van der Pluijm Rebecca Rowe Andrew Lovett Iain Donnison Andreas Kiesel John Clifton-Brown Astley Hastings 《Global Change Biology Bioenergy》2023,15(4):444-461
New biomass crop hybrids for bioeconomic expansion require yield projections to determine their potential for strategic land use planning in the face of global challenges. Our biomass growth simulation incorporates radiation interception and conversion efficiency. Models often use leaf area to predict interception which is demanding to determine accurately, so instead we use low-cost rapid light interception measurements using a simple laboratory-made line ceptometer and relate the dynamics of canopy closure to thermal time, and to measurements of biomass. We apply the model to project the European biomass potentials of new market-ready hybrids for 2020–2030. Field measurements are easier to collect, the calibration is seasonally dynamic and reduces influence of weather variation between field sites. The model obtained is conservative, being calibrated by crops of varying establishment and varying maturity on less productive (marginal) land. This results in conservative projections of miscanthus hybrids for 2020–2030 based on 10% land use conversion of the least (productive) grassland and arable for farm diversification, which show a European potential of 80.7–89.7 Mt year−1 biomass, with potential for 1.2–1.3 EJ year−1 energy and 36.3–40.3 Mt year−1 carbon capture, with seeded Miscanthus sacchariflorus × sinensis displaying highest yield potential. Simulated biomass projections must be viewed in light of the field measurements on less productive land with high soil water deficits. We are attempting to model the results from an ambitious and novel project combining new hybrids across Europe with agronomy which has not been perfected on less productive sites. Nevertheless, at the time of energy sourcing issues, seed-propagated miscanthus hybrids for the upscaled provision of bioenergy offer an alternative source of renewable energy. If European countries provide incentives for growers to invest, seeded hybrids can improve product availability and biomass yields over the current commercial miscanthus variety. 相似文献
145.
146.
Patrick Diep Heping Leo Shen Julian A. Wiesner Nadia Mykytczuk Vladimiros Papangelakis Alexander F. Yakunin Radhakrishnan Mahadevan 《Engineering in Life Science》2023,23(7):2200133
Mine wastewater often contains dissolved metals at concentrations too low to be economically extracted by existing technologies, yet too high for environmental discharge. The most common treatment is chemical precipitation of the dissolved metals using limestone and subsequent disposal of the sludge in tailing impoundments. While it is a cost-effective solution to meet regulatory standards, it represents a lost opportunity. In this study, we engineered Escherichia coli to overexpress its native NikABCDE transporter and a heterologous metallothionein to capture nickel at concentrations in local effluent streams. We found the engineered strain had a 7-fold improvement in the bioaccumulation performance for nickel compared to controls, but also observed a drastic decrease in cell viability due to metabolic burden or inducer (IPTG) toxicity. Growth kinetic analysis revealed the IPTG concentrations used based on past studies lead to growth inhibition, thus delineating future avenues for optimization of the engineered strain and its growth conditions to perform in more complex environments. 相似文献
147.
Evelina L Zdorovenko Evgeny Vinogradov Galina M Zdorovenko Buko Lindner Olga V Bystrova Alexander S Shashkov Klaus Rudolph Ulrich Z?hringer Yuriy A Knirel 《European journal of biochemistry》2004,271(23-24):4968-4977
The core structure of the lipopolysaccharide (LPS) isolated from a rough strain of the phytopathogenic bacterium Pseudomonas syringae pv. phaseolicola, GSPB 711, was investigated by sugar and methylation analyses, Fourier transform ion-cyclotron resonance ESI MS, and one- and two-dimensional 1H-, 13C- and 31P-NMR spectroscopy. Strong alkaline deacylation of the LPS resulted in two core-lipid A backbone undecasaccharide pentakisphosphates in the ratio approximately 2.5 : 1, which corresponded to outer core glycoforms 1 and 2 terminated with either L-rhamnose or 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo), respectively. Mild acid degradation of the LPS gave the major glycoform 1 core octasaccharide and a minor truncated glycoform 2 core heptasaccharide, which resulted from the cleavage of the terminal Kdo residues. The inner core of P. syringae is distinguished by a high degree of phosphorylation of L-glycero-D-manno-heptose residues with phosphate, diphosphate and ethanolamine diphosphate groups. The glycoform 1 core is structurally similar but not identical to one of the core glycoforms of the human pathogenic bacterium Pseudomonas aeruginosa. The outer core composition and structure may be useful as a chemotaxonomic marker for the P. syringae group of bacteria, whereas a more conserved inner core structure appears to be representative for the whole genus Pseudomonas. 相似文献
148.
Alexander N. Banks & Robert B. Srygley 《Ethology : formerly Zeitschrift fur Tierpsychologie》2003,109(10):835-846
Leaf‐cutter ants (Atta colombica) use trail following to travel between foraging sites and the home nest. However, this combination of pheromone and visual cues is likely to be complemented by a directional reference system such as a compass, used not only when foraging but also during colony formation, where foraging trails degrade or where ants become displaced. One candidate system is the magnetic polarity compass. We tested the orientation of leaf‐cutter ants under a magnetic field of reversed‐polarity, with the prediction that the ants would show 180° deflection compared with control ants in an unchanged geomagnetic field. When the sun's disc was unobstructed by clouds, orientation was the same as that of control ants, implying that magnetic cues were not used to orient. However, when the sky was overcast, ants in the experimental treatment significantly shifted their mean orientation both in comparison with controls and reversed‐polarity ants under the sun. Although a total reversal in orientation was not induced, the results demonstrate that Atta respond to magnetic reversal in the absence of sunlight cues, and suggest a role for magnetic cues in determining direction during orientation. 相似文献
149.
Tatyana V Ovchinnikova Zakhar O Shenkarev Zoya A Yakimenko Natalia V Svishcheva Andrey A Tagaev Dmitry A Skladnev Alexander S Arseniev 《Journal of peptide science》2003,9(11-12):817-826
Zervamicin IIB is a member of the alpha-aminoisobutyric acid containing peptaibol antibiotics. A new procedure for the biosynthetic preparation of the uniformly 13C- and 15N-enriched peptaibol is described This compound was isolated from the biomass of the fungus-producer Emericellopsis salmosynnemata strain 336 IMI 58330 obtained upon cultivation in the totally 13C, 15N-labelled complete medium. To prepare such a medium the autolysed biomass and the exopolysaccharides of the obligate methylotrophic bacterium Methylobacillus flagellatus KT were used. This microorganism was grown in totally 13C, 15N-labelled minimal medium containing 13C-methanol and 15N-ammonium chloride as the only carbon and nitrogen sources. Preliminary NMR spectroscopic analysis indicated a high extent of isotope incorporation (> 90%) and led to the complete 13C- and 15N-NMR assignment including the stereospecific assignment of Aib residues methyl groups. The observed pattern of the structurally important secondary chemical shifts of 1H(alpha), 13C=O and 13C(alpha) agrees well with the previously determined structure of zervamicin IIB in methanol solution. 相似文献
150.
Andrzej Slominski Alexander Pisarchik Igor Semak Trevor Sweatman Jacobo Wortsman 《European journal of biochemistry》2003,270(16):3335-3344
We showed expression of the tryptophan hydroxylase gene and of tryptophan hydroxylase protein immunoreactivity in mouse skin and skin cells. Extracts from skin and melanocyte samples acetylated serotonin to N-acetylserotonin and tryptamine to N-acetyltryptamine. A different enzyme from arylalkylamine N-acetyltransferase mediated this reaction, as this gene was defective in the C57BL6 mouse, coding predominantly for a protein without enzymatic activity. Serotonin (but not tryptamine) acetylation varied according to hair cycle phase and anatomic location. Serotonin was also metabolized to 5-hydroxytryptophol and 5-hydroxyindole acetic acid, probably through stepwise transformation catalyzed by monoamine oxidase, aldehyde dehydrogenase and aldehyde reductase. Activity of the melatonin-forming enzyme hydroxyindole-O-methyltransferase was notably below detectable levels in all samples of mouse corporal skin, although it was detectable at low levels in the ears and in Cloudman melanoma (derived from the DBA/2 J mouse strain). In conclusion, mouse skin has the molecular and biochemical apparatus necessary to produce and metabolize serotonin and N-acetylserotonin, and its activity is determined by topography, physiological status of the skin, cell type and mouse strain. 相似文献