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31.
Discovery of novel aspartyl ketone dipeptides as potent and selective caspase-3 inhibitors 总被引:4,自引:0,他引:4
Han Y Giroux A Grimm EL Aspiotis R Francoeur S Bayly CI Mckay DJ Roy S Xanthoudakis S Vaillancourt JP Rasper DM Tam J Tawa P Thornberry NA Paterson EP Garcia-Calvo M Becker JW Rotonda J Nicholson DW Zamboni RJ 《Bioorganic & medicinal chemistry letters》2004,14(3):805-808
The discovery of a series of potent, selective and reversible dipeptidyl caspase-3 inhibitors are reported. The iterative discovery process of using combinatorial chemistry, parallel synthesis, moleculare modelling and structural biology will be discussed. 相似文献
32.
The aerobic acidophilic bacterium Acidithiobacillus ferrooxidans oxidizes Fe(2+) and S(2)O(3)(2-) ions by consuming oxygen. An amperometric biosensor was designed including an oxygen probe as transducer and a recognition element immobilized by a suitable home-made membrane. This biosensor was used for the indirect amperometric determination of Cr(2)O(7)(2-) ions owing to methods based on a mediator (Fe(2+)) or titration. Using the mediator, the biosensor response versus Cr(2)O(7)(2-) was linear up to 0.4 mmol L(-1), with a response time of, respectively, 51 s (2 x 10(-5) mol L(-1) Cr(2)O(7)(2-)) and 61 s (6 x 10(-5) mol L(-1) Cr(2)O(7)(2-)). The method sensitivity was 816 microA L mol(-1). Response time and measurement sensitivity depended on membrane material and technique for biomass immobilization. For example, their values were 90 s-200 microA L mol(-1) when using a glass-felt membrane and 540 s-4.95 microA L mol(-1) with a carbon felt one to determine a concentration of 2 x 10(-5) mol L(-1) Cr(2)O(7)(2-). For the titration method, the biosensor is used to determine the equivalence point. The relative error of quantitative analysis was lower than 5%. 相似文献
33.
Jordi Sala Stéphanie Gascón David Cunillera-Montcusí Miguel Alonso Francisco Amat Luís Cancela da Fonseca Margarida Cristo Margarita Florencio Juan García-de-Lomas Margarida Machado Maria Rosa Miracle Alexandre Miró José Luis Pérez-Bote Joan Lluís Pretus Florent Prunier Javier Ripoll Juan Rueda María Sahuquillo Laura Serrano Marc Ventura David Verdiell-Cubedo Dani Boix 《Hydrobiologia》2017,784(1):81-91
The deficiency in the distributional data of invertebrate taxa is one of the major impediments acting on the bias towards the low awareness of its conservation status. The present study sets a basic framework to understand the large branchiopods distribution in the Iberian Peninsula and Balearic Islands. Since the extensive surveys performed in the late 1980s, no more studies existed updating the information for the whole studied area. The present study fills the gap, gathering together all available information on large branchiopods distribution since 1995, and analysing the effect of human population density and several landscape characteristics on their distribution, taking into consideration different spatial scales (100 m, 1 km and 10 km). In overall, 28 large branchiopod taxa (17 anostracans, 7 notostracans and 4 spinicaudatans) are known to occur in the area. Approximately 30% of the sites hosted multiple species, with a maximum of 6 species. Significant positive co-occurring species pairs were found clustered together, forming 4 different associations of large branchiopod species. In general, species clustered in the same group showed similar responses to analysed landscape characteristics, usually showing a better fit at higher spatial scales. 相似文献
34.
Valakos ED Kourkouli A Skopeliti M Pafilis P Poulakakis N Voutsas IF Lymberakis P Simou C Voelter W Tsitsilonis OE 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2007,147(1):1-10
Most recent molecular studies revealed the phylogeny of Greek Podarcis species, which for years remained elusive, due to discordant data produced from various chromosomal, complement fixation and protein studies. In this report, we analyzed cellular immune responses of spleen-derived lymphocytes from six allopatric Podarcis species encountered in Greece, by assessing two-way mixed lymphocyte reaction (MLR)-induced proliferation. On the basis of stimulation indices (S.I.) as determined from cultures set up from xenogeneic splenocytes coincubated in pairs, we generated a phylogenetic tree, fully consistent with the phylogenetic relationships of Podarcis as determined by parallel analyses based on partial mitochondrial (mt) DNA sequences. Although the exact mechanisms triggering lymphocyte responses in lizard two-way xenogeneic MLR are not fully understood, our results show the potential use of cell-mediated immune responses as an additional approach to mtDNA analysis, for species delimitation within specific lizard taxa. 相似文献
35.
Terrasa AM Guajardo MH de Armas Sanabria E Catalá A 《Biochimica et biophysica acta》2005,1735(2):101-110
Reactive oxygen species play an important role in several acute lung injuries. The lung tissue contains polyunsaturated fatty acids (PUFAs) that are substrates of lipid peroxidation that may lead to loss of the functional integrity of the cell membranes. In this study, we compare the in vitro protective effect of pulmonary surfactant protein A (SP-A), purified from porcine surfactant, against ascorbate-Fe(2+) lipid peroxidation stimulated by linoleic acid hydroperoxide (LHP) of the mitochondria and microsomes isolated from rat lung; deprived organelles of ascorbate and LHP were utilized as control. The process was measured simultaneously by chemiluminescence as well as by PUFA degradation of the total lipids isolated from these organelles. The addition of LHP to rat lung mitochondria or microsomes produces a marked increase in light emission; the highest value of activation was produced in microsomes (total chemiluminescence: 20.015+/-1.735 x 10(5) cpm). The inhibition of lipid peroxidation (decrease of chemiluminescence) was observed with the addition of increasing amounts (2.5 to 5.0 microg) of SP-A in rat lung mitochondria and 2.5 to 7.5 microg of SP-A in rat lung microsomes. The inhibitory effect reaches the highest values in the mitochondria, thus, 5.0 microg of SP-A produces a 100% inhibition in this membranes whereas 7.5 microg of SP-A produces a 51.25+/-3.48% inhibition in microsomes. The major difference in the fatty acid composition of total lipids isolated from native and peroxidized membranes was found in the arachidonic acid content; this decreased from 9.68+/-1.60% in the native group to 5.72+/-1.64% in peroxidized mitochondria and from 7.39+/-1.14% to 3.21+/-0.77% in microsomes. These changes were less pronounced in SP-A treated membranes; as an example, in the presence of 5.0 microg of SP-A, we observed a total protection of 20:4 n-6 (9.41+/-3.29%) in mitochondria, whereas 7.5 microg of SP-A produced a 65% protection in microsomes (5.95+/-0.73%). Under these experimental conditions, SP-A produces a smaller inhibitory effect in microsomes than in mitochondria. Additional studies of lipid peroxidation of rat lung mitochondria or microsomes using equal amounts of albumin and even higher compared to SPA were carried out. Our results indicate that under our experimental conditions, BSA was unable to inhibit lipid peroxidation stimulated by linoleic acid hydroperoxide of rat lung mitochondria or microsomes, thus indicating that this effect is specific to SP-A. 相似文献
36.
Margarita A. Marchenkova Vladimir I. Timofeev Anastasiia S. Boikova Pavel V. Dorovatovskii Yulia A. Dyakova 《Journal of biomolecular structure & dynamics》2020,38(17):5159-5172
AbstractThe bonds between lysozyme molecules and precipitant ions in single crystals grown with chlorides of several metals are analysed on the basis of crystal structure data. Crystals of tetragonal hen egg lysozyme (HEWL) were grown with chlorides of several alkali and transition metals (LiCl, NaCl, KCl, NiCl2 and CuCl2) as precipitants and the three-dimensional structures were determined at 1.35?Å resolution by X-ray diffraction method. The positions of metal and chloride ions attached to the protein were located, divided into three groups and analysed. Some of them, in accordance with the recently proposed and experimentally confirmed crystal growth model, provide connections in protein dimers and octamers that are precursor clusters in the crystallization lysozyme solution. The first group, including Cu+2, Ni+2 and Na+1 cations, binds specifically to the protein molecule. The second group consists of metal and chloride ions bound inside the dimers and octamers. The third group of ions can participate in connections between the octamers that are suggested as building units during the crystal growth. The arrangement of chloride and metal ions associated with lysozyme molecule at all stages of the crystallization solution formation and crystal growth is discussed.Communicated by Ramaswamy H. Sarma 相似文献
37.
Jaime Carrasco Carlos García-Delgado Rebeca Lavega María L. Tello María De Toro Víctor Barba-Vicente María S. Rodríguez-Cruz María J. Sánchez-Martín Margarita Pérez Gail M. Preston 《Microbial biotechnology》2020,13(6):1933-1947
Microorganisms strongly influence and are required to generate the selective substrate that provides nutrients and support for fungal growth, and ultimately to induce mushroom fructification under controlled environmental conditions. In this work, the fungal and bacterial microbiota living in the different substrates employed in a commercial crop (compost phase I, II and III, flush 1 and 2, and casing material on day 1, 6 and 8 after compost casing and during flush 1 and 2) have been characterized along the different stages of cultivation by metataxonomic analysis (16S rRNA and ITS2), analysis of phospholipid fatty acid content (PLFAs) and RT-qPCR. Additionally, laccase activity and the content of lignin and complex carbohydrates in compost and casing have been quantified. The bacterial diversity in compost and casing increased throughout the crop cycle boosted by the connection of both substrates. As reflected by the PLFAs, the total living bacterial biomass appears to be negatively correlated with the mycelium of the crop. Agaricus bisporus was the dominant fungal species in colonized substrates, displacing the pre-eminent Ascomycota, accompanied by a sustained increase in laccase activity, which is considered to be a major product of protein synthesis during the mycelial growth of champignon. From phase II onwards, the metabolic machinery of the fungal crop degrades lignin and carbohydrates in compost, while these components are hardly degraded in casing, which reflects the minor role of the casing for nourishing the crop. The techniques employed in this study provide a holistic and detailed characterization of the changing microbial composition in commercial champignon substrates. The knowledge generated will contribute to improve compost formulations (selection of base materials) and accelerate compost production, for instance, through biotechnological interventions in the form of tailored biostimulants and to design environmentally sustainable bio-based casing materials. 相似文献
38.
Arun T. John Peter Jens Lachmann Meenakshi Rana Madeleine Bunge Margarita Cabrera Christian Ungermann 《The Journal of cell biology》2013,201(1):97-111
Membrane microcompartments of the early endosomes serve as a sorting and signaling platform, where receptors are either recycled back to the plasma membrane or forwarded to the lysosome for destruction. In metazoan cells, three complexes, termed BLOC-1 to -3, mediate protein sorting from the early endosome to lysosomes and lysosome-related organelles. We now demonstrate that BLOC-1 is an endosomal Rab-GAP (GTPase-activating protein) adapter complex in yeast. The yeast BLOC-1 consisted of six subunits, which localized interdependently to the endosomes in a Rab5/Vps21-dependent manner. In the absence of BLOC-1 subunits, the balance between recycling and degradation of selected cargoes was impaired. Additionally, our data show that BLOC-1 is both a Vps21 effector and an adapter for its GAP Msb3. BLOC-1 and Msb3 interacted in vivo, and both mutants resulted in a redistribution of active Vps21 to the vacuole surface. We thus conclude that BLOC-1 controls the lifetime of active Rab5/Vps21 and thus endosomal maturation along the endocytic pathway. 相似文献
39.
Motura MI Moroni GN Teijeiro SA Salomón H Briñón MC 《Nucleosides, nucleotides & nucleic acids》2002,21(3):217-230
Synthesis, solid state characterization and anti HIV-1 activity of 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine (2), a new prodrug of zidovudine (AZT, 1), are described. Two solid forms of 2 prepared by crystallization from ethyl acetate-petroleum ether (form alpha) and from a melt sample of form alpha (amorphous form) were characterized by X-ray diffractometry, infrared spectroscopy, differential scanning calorimetry (DSC) and thermogravimetry (TGA) techniques. The novel nucleoside exhibited antiviral activity against standard and resistant strain panels of HIV-1 as well as cytotoxicity similar to that of AZT. 相似文献
40.