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排序方式: 共有85条查询结果,搜索用时 46 毫秒
31.
Natasha Kruglyak David E. Williams Henry Chen Simon Law Jadwiga Kaleta Ivan Villanueva Julian E. Davies Raymond J. Andersen Dieter Brömme 《Bioorganic & medicinal chemistry letters》2017,27(6):1397-1400
Using a human cathepsin K-targeting inhibitor screen, a new leupeptin analogue, leupeptazin (1), containing an unprecedented piperidinotriazine moiety, was isolated from a liquid culture of soil Streptomyces sp. IS2-4 collected in northern Italy. The structure of leupeptazin was established using HRESIMS as well as 1D and 2D NMR data. The inhibitory activity of the compound towards the collagenase cathepsin K was tested in vitro to reveal moderate activity with an inhibition constant, Ki, of 44 μM. 相似文献
32.
Isolation and characterization of a hepatitis B virus endemic in herons. 总被引:13,自引:21,他引:13
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A new hepadnavirus (designated heron hepatitis B virus [HHBV]) has been isolated; this virus is endemic in grey herons (Ardea cinerea) in Germany and closely related to duck hepatitis B virus (DHBV) by morphology of viral particles and size of the genome and of the major viral envelope and core proteins. Despite its striking similarities to DHBV, HHBV cannot be transmitted to ducks by infection or by transfection with cloned viral DNA. After the viral genome was cloned and sequenced, a comparative sequence analysis revealed an identical genome organization of HHBV and DHBV (pre-C/C-, pre-S/S-, and pol-ORFs). An open reading frame, designated X in mammalian hepadnaviruses, is not present in DHBV. DHBV and HHBV differ by 21.6% base exchanges, and thus they are less closely related than the two known rodent hepatitis B viruses (16.4%). The nucleocapsid protein and the 17-kilodalton envelope protein sequences of DHBV and HHBV are well conserved. In contrast, the pre-S part of the 34-kilodalton envelope protein which is believed to mediate virus attachment to the cell is highly divergent (less than 50% homology). The availability of two closely related avian hepadnaviruses will now allow us to test recombinant viruses in vivo and in vitro for host specificity-determining sequences. 相似文献
33.
Influence of some inhibitors of histamine metabolism on the gastric secretion. Acta Physiol. Pol., 1977, 28 (6): 515-520. The influence of inhibitors of histamine metabolism on histamine (H) and Nalpha Nalpha-dimethylhistamine (NDMH) stimulated gastric secretion was studied in guinea-pigs and cats. Inhibitors of monoamine oxidase (MAO) and diamine oxidase (DAO): N-oxide diacetylaminopyridine (AAP) and N-oxide 2 aminopyridine (AP) increased HCI secretion in the gastric juice after H and NDMH. Inhibitors of N-methyl transferase: amodiaquine (A) and quinacrine (Q) increased HC1 secretion in the gastric juice after H but not after NDMH. The lack of action of A and Q on NDMH-stimulated gastric secretion suggests, that in guinea-pig and cat NDMH is not methylated additionally at the imidazole ring and therefore, it is a stronger gastric secretagogue than histamine itself. 相似文献
34.
Dorota Łażewska Maria Kaleta Stefanie Hagenow Szczepan Mogilski Gniewomir Latacz Tadeusz Karcz Annamaria Lubelska Ewelina Honkisz Jadwiga Handzlik David Reiner Grzegorz Satała Barbara Filipek Holger Stark Katarzyna Kieć-Kononowicz 《Bioorganic & medicinal chemistry》2018,26(9):2573-2585
A series of 1- and 2-naphthyloxy derivatives were synthesized and evaluated for histamine H3 receptor affinity. Most compounds showed high affinities with Ki values below 100?nM. The most potent ligand, 1-(5-(naphthalen-1-yloxy)pentyl)azepane (11) displayed high affinity for the histamine H3 receptor with a Ki value of 21.9?nM. The antagonist behaviour of 11 was confirmed both in vitro in the cAMP assay (IC50?=?312?nM) and in vivo in the rat dipsogenia model (ED50?=?3.68?nM). Moreover, compound 11 showed positive effects on scopolamine induced-memory deficits in mice (at doses of 10 and 15?mg/kg) and an analgesic effect in the formalin test in mice with ED50?=?30.6?mg/kg (early phase) and ED50?=?20.8?mg/kg (late phase). Another interesting compound, 1-(5-(Naphthalen-1-yloxy)pentyl)piperidine (13; H3R Ki?=?53.9?nM), was accepted for Anticonvulsant Screening Program at the National Institute of Neurological Disorders and Stroke/National Institute of Health (Rockville, USA). The screening was performed in the maximal electroshock seizure (MES), the subcutaneous pentylenetetrazole (scPTZ) and the 6-Hz psychomotor animal models of epilepsy. Neurologic deficit was evaluated by the rotarod test. Compound 13 inhibited convulsions induced by the MES with ED50 of 19.2?mg/kg (mice, i.p.), 17.8 (rats, i.p.), and 78.1 (rats, p.o.). Moreover, 13 displayed protection against the 6-Hz psychomotor seizures (32?mA) in mice (i.p.) with ED50 of 33.1?mg/kg and (44?mA) ED50 of 57.2?mg/kg.Furthermore, compounds 11 and 13 showed in vitro weak influence on viability of tested cell lines (normal HEK293, neuroblastoma IMR-32, hepatoma HEPG2), weak inhibition of CYP3A4 activity, and no mutagenicity. Thus, these compounds may be used as leads in a further search for histamine H3 receptor ligands with promising in vitro and in vivo activity. 相似文献
35.
Zhou NE Kaleta J Purisima E Menard R Micetich RG Singh R 《Bioorganic & medicinal chemistry letters》2002,12(23):3417-3419
The synthesis of a new series of 6-acylamino penam derivatives and their inhibition of cysteine proteases cathepsins B, L, K, and S is described. The 6-acylamino-penam sulfone compounds showed excellent cathepsin L, K, and S inhibition activity with IC(50) values in the nanomolar and subnanomolar range. 相似文献
36.
Pathways are typically the central concept in the analysis of biochemical reaction networks. A pathway can be interpreted as a chain of enzymatical reactions performing a specific biological function. A common way to study metabolic networks are minimal pathways that can operate at steady state called elementary modes. The theory of chemical organizations has recently been used to decompose biochemical networks into algebraically closed and self-maintaining subnetworks termed organizations. The aim of this paper is to elucidate the relation between these two concepts. Whereas elementary modes represent the boundaries of the potential behavior of the network, organizations define metabolite compositions that are likely to be present in biological feasible situations. Hence, steady state organizations consist of combinations of elementary modes. On the other hand, it is possible to assign a unique (and possibly empty) set of organizations to each elementary mode, indicating the metabolites accompanying the active pathway in a feasible steady state. 相似文献
37.
Katharina Kaleta 《Inorganica chimica acta》2011,370(1):187-190
The alkyne complexes [Cp′2M(L)(η2-Me3SiC2SiMe3)] (Cp′ = substituted or unsubstituted cyclopentadienyl; M = Ti, Zr, Hf; L = Py, THF) can serve as metallocene precursors by substitution of the alkyne molecule with other ligands. The reactions of the unsubstituted cyclopentadienyl complexes [Cp2Zr(THF)(η2-Me3SiC2SiMe3)] (1) and [Cp2Ti(η2-Me3SiC2SiMe3)] (2) with azobenzene were investigated. In the first case the diazene complex [Cp2Zr(THF)(N2Ph2)] (3) was obtained by alkyne exchange. In the reaction of the titanium complex 2 a NN bond cleavage of azobenzene and a C-H activation of the cyclopentadienyl ligand were observed and the dinuclear imido bridged compound 4 was formed. This mixed valence complex is bridged additionally by a cyclopentadienyl ligand in a η1:η5-coordination mode which is very unusual for titanium complexes. The molecular structures of both compounds were confirmed by X-ray crystallography and compared to former structural data shown in literature. 相似文献
38.
Beuster G Zarse K Kaleta C Thierbach R Kiehntopf M Steinberg P Schuster S Ristow M 《The Journal of biological chemistry》2011,286(25):22323-22330
Cancer cells commonly exhibit increased nonoxidative D-glucose metabolism whereas induction of mitochondrial metabolism may impair malignant growth. We have first used an in silico method called elementary mode analysis to identify inhibition of ALAT (L-alanine aminotransferase) as a putative target to promote mitochondrial metabolism. We then experimentally show that two competitive inhibitors of ALAT, L-cycloserine and β-chloro-L-alanine, inhibit L-alanine production and impair D-glucose uptake of LLC1 Lewis lung carcinoma cells. The latter inhibition is linked to an initial energy deficit, as quantified by decreased ATP content, which is then followed by an activation of AMP-activated protein kinase and subsequently increased respiration rates and mitochondrial production of reactive oxygen species, culminating in ATP replenishment in ALAT-inhibited LLC1 cells. Moreover, we observe altered phosphorylation of p38 MAPK (mitogen-activated protein kinase 14), ERK (extracellular signal-regulated kinase 1/2), and Rb1 (retinoblastoma 1) proteins, as well as decreased expression of Cdc25a (cell decision cycle 25 homolog A) and Cdk4 (cyclin-dependent kinase 4). Importantly, these sequelae of ALAT inhibition culminate in similarly reduced anchorage-dependent and anchorage-independent growth rates of LLC1 cells, together suggesting that inhibition of ALAT efficiently impairs cancer growth by counteracting the Warburg effect due to compensatory activation of mitochondrial metabolism. 相似文献
39.
Samay Pande Holger Merker Katrin Bohl Michael Reichelt Stefan Schuster Luís F de Figueiredo Christoph Kaleta Christian Kost 《The ISME journal》2014,8(5):953-962
Cross-feeding interactions, in which bacterial cells exchange costly metabolites to the benefit of both interacting partners, are very common in the microbial world. However, it generally remains unclear what maintains this type of interaction in the presence of non-cooperating types. We investigate this problem using synthetic cross-feeding interactions: by simply deleting two metabolic genes from the genome of Escherichia coli, we generated genotypes that require amino acids to grow and release other amino acids into the environment. Surprisingly, in a vast majority of cases, cocultures of two cross-feeding strains showed an increased Darwinian fitness (that is, rate of growth) relative to prototrophic wild type cells—even in direct competition. This unexpected growth advantage was due to a division of metabolic labour: the fitness cost of overproducing amino acids was less than the benefit of not having to produce others when they were provided by their partner. Moreover, frequency-dependent selection maintained cross-feeding consortia and limited exploitation by non-cooperating competitors. Together, our synthetic study approach reveals ecological principles that can help explain the widespread occurrence of obligate metabolic cross-feeding interactions in nature. 相似文献
40.
Brigitte M. Bönner Walburga Lutz Sabine Jäger T. Redmann B. Reinhardt U. Reichel V. Krajewski R. Weiss J. Wissing W. Knickmeier W. H. Gerlich Ulrike C. Wend E. F. Kaleta 《European Journal of Wildlife Research》2004,50(2):78-84
Currently, large groups of Canada geese (Branta canadensis Linnaeus, 1758) aggregate in recreational areas of north-western Germany. Questions have arisen as to whether these birds represent a special risk factor as a source of zoonotic agents for humans and as a source of viruses, causing notifiable or reportable diseases, for domestic poultry and waterfowl. To answer these questions, a total of 289 eggs were collected in 2002 and 2003 on a recreation site and assayed. Chlamydia psittaci was not isolated and neither was chlamydial antigen detected by polymerase chain reaction. All virus-isolation attempts were unsuccessful. Neither Salmonella spp. nor Campylobacter spp. was isolated from embryonic tissues, chorioallantoic membranes or yolk-sac membranes. The presence of antibodies against Newcastle disease virus and influenza A virus (haemagglutinin subtypes H5 and H7) was demonstrated in egg yolk. Antibodies were also detected against the egg-drop syndrome 1976 and duck plague viruses. It is concluded that further surveillance studies are needed for a reliable risk assessment. 相似文献