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101.
Zoltán Nemes Krisztina Takács-Novák Gergely Völgyi Klara Valko Szabolcs Béni Zoltán Horváth Bálint Szokol Nóra Breza Judit Dobos Csaba Szántai-Kis Eszter Illyés Sándor Boros Robbert Jan Kok László Őrfi 《Bioorganic & medicinal chemistry letters》2018,28(14):2391-2398
Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Sunitinib, a multikinase inhibitor, was the first Fms-like tyrosine kinase 3 (FLT3) inhibitor clinically used against AML. Off-target effects are a major concern for multikinase inhibitors. As targeted delivery may reduce such undesired side effects, our goal was to develop novel amino acid substituted derivatives of sunitinib which are potent candidates to be used conjugated with antibodies and peptides. In the current paper we present the synthesis, physicochemical and in vitro characterization of sixty two Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutant kinase inhibitors, bearing amino acid moieties, fit to be conjugated with peptide-based delivery systems via their carboxyl group. We determined the solubility, pKa, CHI and LogP values of the compounds along with their inhibition potential against FLT3-ITD mutant kinase and on MV4-11 cell line. The ester derivatives of the compounds inhibit the growth of the MV4-11 leukemia cell line at submicromolar concentration. 相似文献
102.
Elongation factor Tu: a molecular switch in protein biosynthesis 总被引:5,自引:0,他引:5
Albert Weijland Kim Harmark Robbert H. Cool † Pieter H. Anborgh rea Parmeggiani 《Molecular microbiology》1992,6(6):683-688
Elongation factor Tu (EF-Tu), the most abundant protein in Escherichia coli, is a guanine nucleotide-binding protein that in the 'on' state acts as a carrier of amino acyl-tRNA to the ribosome. Our knowledge of this essential component of translation has brought substantial progress in the past decade thanks to the co-ordinated application of biochemical, physico-chemical and genetic methods. Crystallographic analysis at 2.6 A resolution and site-directed mutagenesis have revealed structural and functional similarities between the guanine nucleotide-binding domains of EF-Tu and human H-ras p21 protein. The regulation of the expression of the two EF-Tu-encoding genes in E. coli, particularly that of tufB, has been shown to involve diverse mechanisms. Several aspects of the functions of EF-Tu in the elongation cycle have been reinvestigated, leading to new insights. These studies have emphasized the manifold aspects of the mechanisms regulating the activity of EF-Tu in the bacterial cell. 相似文献
103.
104.
Bassin JP Kleerebezem R Muyzer G Rosado AS van Loosdrecht MC Dezotti M 《Applied microbiology and biotechnology》2012,93(3):1281-1294
The effect of salinity on the activity of nitrifying bacteria, floc characteristics, and microbial community structure accessed
by fluorescent in situ hybridization and polymerase chain reaction–denaturing gradient gel electrophoresis techniques was
investigated. Two sequencing batch reactors (SRB1 and SBR2) treating synthetic wastewater were subjected to increasing salt concentrations. In SBR1, four salt concentrations (5, 10, 15, and 20 g NaCl/L) were tested, while in SBR2, only two salt concentrations (10 and 20 g NaCl/L) were applied in a more shock-wise manner. The two different salt adaptation
strategies caused different changes in microbial community structure, but did not change the nitrification performance, suggesting
that regardless of the different nitrifying bacterial community present in the reactor, the nitrification process can be maintained
stable within the salt range tested. Specific ammonium oxidation rates were more affected when salt increase was performed
more rapidly and dropped 50% and 60% at 20 g NaCl/L for SBR1 and SBR2, respectively. A gradual increase in NaCl concentration had a positive effect on the settling properties (i.e., reduction
of sludge volume index), although it caused a higher amount of suspended solids in the effluent. Higher organisms (e.g., protozoa,
nematodes, and rotifers) as well as filamentous bacteria could not withstand the high salt concentrations. 相似文献
105.
106.
Impending local extinction of Aloe ferox Mill. populations in the absence of elephants and black rhinos? 下载免费PDF全文
107.
Dick Tibboel Annelies de Klein Robbert J. Rottier 《Birth defects research. Part C, Embryo today : reviews》2014,102(4):343-358
Pulmonary vascular diseases of the newborn comprise a wide range of pathological conditions with developmental abnormalities in the pulmonary vasculature. Clinically, pulmonary arterial hypertension (PH) is characterized by persistent increased resistance of the vasculature and abnormal vascular response. The classification of PH is primarily based on clinical parameters instead of morphology and distinguishes five groups of PH. Congenital lung anomalies, such as alveolar capillary dysplasia (ACD) and PH associated with congenital diaphragmatic hernia (CDH), but also bronchopulmonary dysplasia (BPD), are classified in group three. Clearly, tight and correct regulation of pulmonary vascular development is crucial for normal lung development. Human and animal model systems have increased our knowledge and make it possible to identify and characterize affected pathways and study pivotal genes. Understanding of the normal development of the pulmonary vasculature will give new insights in the origin of the spectrum of rare diseases, such as CDH, ACD, and BPD, which render a significant clinical problem in neonatal intensive care units around the world. In this review, we describe normal pulmonary vascular development, and focus on four diseases of the newborn in which abnormal pulmonary vascular development play a critical role in morbidity and mortality. In the future perspective, we indicate the lines of research that seem to be very promising for elucidating the molecular pathways involved in the origin of congenital pulmonary vascular disease. Birth Defects Research (Part C) 102:343–358, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
108.
Dröge MJ Boersma YL Braun PG Buining RJ Julsing MK Selles KG van Dijl JM Quax WJ 《Applied and environmental microbiology》2006,72(7):4589-4595
Using the phage display technology, a protein can be displayed at the surface of bacteriophages as a fusion to one of the phage coat proteins. Here we describe development of this method for fusion of an intracellular carboxylesterase of Bacillus subtilis to the phage minor coat protein g3p. The carboxylesterase gene was cloned in the g3p-based phagemid pCANTAB 5E upstream of the sequence encoding phage g3p and downstream of a signal peptide-encoding sequence. The phage-bound carboxylesterase was correctly folded and fully enzymatically active, as determined from hydrolysis of the naproxen methyl ester with Km values of 0.15 mM and 0.22 mM for the soluble and phage-displayed carboxylesterases, respectively. The signal peptide directs the encoded fusion protein to the cell membrane of Escherichia coli, where phage particles are assembled. In this study, we assessed the effects of several signal peptides, both Sec dependent and Tat dependent, on the translocation of the carboxylesterase in order to optimize the phage display of this enzyme normally restricted to the cytoplasm. Functional display of Bacillus carboxylesterase NA could be achieved when Sec-dependent signal peptides were used. Although a Tat-dependent signal peptide could direct carboxylesterase translocation across the inner membrane of E. coli, proper assembly into phage particles did not seem to occur. 相似文献
109.
Kumaraswamy R Kuenen JG Kleerebezem R van Loosdrecht MC Muyzer G 《Applied microbiology and biotechnology》2006,73(4):922-931
BioDeNOx is a combined physicochemical and biological process for the removal of nitrogen oxides (NOx) from flue gas. In the present study, two anaerobic bioreactors performing BioDeNOx were run consecutively (RUN-1 and RUN-2) at a dilution rate of 0.01 h−1 with Fe(II)EDTA.NO2− and Fe(III)EDTA− as electron acceptors and ethanol as electron donor. The measured protein concentration of the reactor biomass of both runs was 120 mg/l. Different molecular methods were used to determine the identity and abundance of the bacterial populations in both bioreactors. Bacillus azotoformans strain KT-1 was recognized as a key player in Fe(II)EDTA.NO2− reduction. PCR-denaturing gradient gel electrophoresis analysis of the reactor biomass showed a greater diversity in RUN-2 than in RUN-1. Enrichments of Fe(II)EDTA.NO2− and Fe(III)EDTA− reducers and activity assays were conducted using the biomass from RUN-2 as an inoculum. The results on substrate turnover, overall microbial diversity, and enrichments and finally activity assays confirmed that ethanol was used as electron donor for Fe(II)EDTA.NO2− reduction. In addition, the Fe(III)EDTA− reduction rate of the microbial community proved to be feasible enough to run the bioreactors, ruling out the chemical reduction of Fe(III)EDTA− with sulfide as was proposed by other researchers. 相似文献
110.
Lipase catalyzed copolymerization of the monomers lactide and glycolide by Pseudomonas cepacia employing a molar ratio of 80L/20G has been studied. The copolymers were characterized by MALDI-ToF-MS, DSC, SEC and NMR. MALDI-ToF-MS has successfully been used not only to determine end groups and chemical composition but even the microstructure of the copolymers. We demonstrated that for this lipase catalyzed copolymerization, the main product of the reaction at 100 degrees C was linear homopolymer of lactide while at 130 degrees C the main product was cyclic random copolymer. 相似文献