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排序方式: 共有190条查询结果,搜索用时 823 毫秒
21.
Duan M Peckham J Edelstein M Ferris R Kazmierski WM Spaltenstein A Wheelan P Xiong Z 《Bioorganic & medicinal chemistry letters》2010,20(24):7401-7404
Modification of the acyl moiety in the CCR5 lead molecule 2 led to identification of several new classes of CCR5 antagonists. Antiviral activity and pharmacokinetic properties of the synthesized compounds were evaluated. Structure-activity relationship (SAR) derived from these studies further guided the optimization efforts, ultimately leading to the discovery of 36 with an acceptable drug-like profile. 相似文献
22.
Legall H Stiel H Beck M Leupold D Gruszecki WI Lokstein H 《Journal of biochemical and biophysical methods》2007,70(3):369-376
Peridinin-chlorophyll a protein (PCP) is a unique water soluble antenna complex that employs the carotenoid peridinin as the main light-harvesting pigment. In the present study the near edge X-ray absorption fine structure (NEXAFS) spectrum of PCP was recorded at the carbon K-edge. Additionally, the NEXAFS spectra of the constituent pigments, chlorophyll a and peridinin, were measured. The energies of the lowest unoccupied molecular levels of these pigments appearing in the carbon NEXAFS spectrum were resolved. Individual contributions of the pigments and the protein to the measured NEXAFS spectrum of PCP were determined using a “building block” approach combining NEXAFS spectra of the pigments and the amino acids constituting the PCP apoprotein. The results suggest that absorption changes of the pigments in the carbon near K-edge region can be resolved following excitation using a suitable visible pump laser pulse. Consequently, it may be possible to study excitation energy transfer processes involving “optically dark” states of carotenoids in pigment-protein complexes by soft X-ray probe optical pump double resonance spectroscopy (XODR). 相似文献
23.
Antosiewicz J Ziolkowski W Kaczor JJ Herman-Antosiewicz A 《Free radical biology & medicine》2007,43(2):265-270
Tumor necrosis factor alpha induces increased reactive oxygen species (ROS) generation in different experimental models. However, the nature of this phenomenon is still unknown. We hypothesized that TNF-induced ROS formation is due to JNK-regulated ferritin degradation and an increase in labile iron pool (LIP). We used as a model human prostate cancer cells, DU145. TNF treatment induced ROS formation, which was reduced to the control level in cells pretreated with desferrioxamine, an iron chelator. TNF induced a drop in light chain of the ferritin level, as judged by immunoblotting and an increase in LIP, evaluated by calcein fluorescence. Moreover, we observed that the JNK inhibitor SP600125 abolished TNF-induced changes in LIP, which suggests that JNK kinases are involved in this process. To explore which one of the JNK kinases is responsible for these effects, DU145 cells were transiently transfected with plasmids encoding inactive mutants of JNK1 or JNK2. The cells expressing inactive JNK1 mutant, but not cells expressing JNK2 mutant or possessing an empty vector, were completely resistant to TNF-induced ROS generation, ferritin degradation, and an increase in LIP. These data suggest that TNF-induced ROS formation is mediated by JNK1, which regulates ferritin degradation and thus the level of highly reactive iron. 相似文献
24.
Duan M Kazmierski WM Chong PY Deanda F Edelstein M Ferris R Peckham J Wheelan P Xiong Z Zhang H Nishizawa R Takaoka Y 《Bioorganic & medicinal chemistry letters》2011,21(21):6470-6475
A novel series of pyridyl carboxamide-based CCR5 inhibitors was designed, synthesized, and demonstrated to be highly potent against HIV-1 infection in both HOS and PBL assays. Attempts to evaluate this series of compounds in a rat PK model revealed its instability in rat plasma. A hypothesis for this liability was proposed, and strategies to overcome this issue were pursued, leading to discovery of highly potent 40 and 41, which featured dramatically improved rat PK profiles. 相似文献
25.
Tallant MD Duan M Freeman GA Ferris RG Edelstein MP Kazmierski WM Wheelan PJ 《Bioorganic & medicinal chemistry letters》2011,21(5):1394-1398
We describe the synthesis and potency of a novel series of N-substituted 2-phenyl- and 2-methyl-2-phenyl-1,4-diaminobutane- based CCR5 antagonists. Compounds 7a and 12f were found to be potent in anti-HIV assays and bioavailable in the low-dose rat PK model. 相似文献
26.
Beata Olas Joanna Kołodziejczyk-Czepas Barbara Wachowicz Dariusz Jędrejek Anna Stochmal Wiesław Oleszek 《Central European Journal of Biology》2011,6(6):990-996
Humulus lupulus (Cannabaceae) is well known throughout the world as a raw material in the brewing industry. The antioxidative action of hop cones is poorly
understood, therefore the aim of our present study was to investigate in vitro changes in human plasma induced by peroxynitrite in the presence of the highly purified extract from hop cones (Humulus lupulus). The aim of our study was also to explain the effect of the extract from hop cones on coagulation activity of human plasma
treated with peroxynitrite. The action of the extract from hop cones was compared with the properties of a well-characterized
commercial monomeric polyphenol — resveratrol (3,4′,5-trihydroxystilbene). The tested plant extract, like resveratrol, significantly
inhibited protein carbonylation and nitration in plasma treated with ONOO−(0.1 mM). The extract from hop cones, like resveratrol, also caused a distinct reduction of plasma lipid peroxidation induced
by ONOO−. Moreover, the tested extract modulated the coagulation properties of plasma treated with peroxynitrite. It seems that antioxidative
activities of the highly purified extract from hop cones may be responsible for its medicinal properties. 相似文献
27.
The ratios between frequency components of evoked otoacoustic emissions (OAE) were investigated for 100 ears. The signals
were decomposed by means of an adaptive approximation method into basic waveforms coming from a very large and redundant dictionary
of Gabor functions. The high time-frequency resolution of the method and the parametric representation of the waveforms allowed
for an estimation of the frequency ratios of the basic components. A repetitive occurrence of the “fifths”, “fourths” and
octaves connected with the Pythagorean temperament was found. The octaves containing “fifths” were identified. This kind of
sequences in OAE tend to appear in the same form for tonal stimulations of different frequencies and for broadband stimuli.
The significance of the results was confirmed by comparison to Monte Carlo simulations of the null hypothesis of random distribution
of frequency modes. These findings support the resonance theory of hearing, which binds musical ratios with the geometrical
spacing of outer hair cells in the cochlea. 相似文献
28.
Recent technical advances have revitalized cell-free expression systems to meet the increasing demands for protein synthesis. Cell-free systems offer several advantages over traditional cell-based expression methods, including the easy modification of reaction conditions to favor protein folding, decreased sensitivity to product toxicity and suitability for high-throughput strategies because of reduced reaction volumes and process time. Moreover, improvements in translation efficiency have resulted in yields that exceed a milligram of protein per milliliter of reaction mix. We review the advances on this expanding technology and highlight the growing list of associated applications. 相似文献
29.
Yersinia pestis Yop secretion protein F: purification, characterization, and protective efficacy against bubonic plague 总被引:1,自引:0,他引:1
Yersinia pestis is a gram-negative human pathogen that uses a type III secretion system to deliver virulence factors into human hosts. The delivery is contact-dependent and it has been proposed that polymerization of Yop secretion protein F (YscF) is used to puncture mammalian cell membranes to facilitate delivery of Yersinia outer protein effectors into host cells. To evaluate the potential immunogenicity and protective efficacy of YscF against Y. pestis, we used a purified recombinant YscF protein as a potential vaccine candidate in a mouse subcutaneous infection model. YscF was expressed and purified from Escherichia coli by immobilized metal-ion affinity chromatography and protein identity was confirmed by ion trap mass spectrometry. The recombinant protein was highly alpha-helical and formed relatively stable aggregates under physiological conditions. The properties were consistent with behavior expected for the native YscF, suggesting that the antigen was properly folded. Ten mice were inoculated subcutaneously, administered booster injections after one month, and challenged with 130 LD(50) of wild type Y. pestis CO92. Six animals in the vaccinated group but none in the control group survived the challenge. The vaccinated animals produced high levels of specific antibodies against YscF as determined by Western blot. The data were statistically significant (P = 0.053 by two-tailed Fisher's test), suggesting that the YscF protein can provide a protective immune response against lethal plague challenge during subcutaneous plague infection. 相似文献
30.
Woclawek-Potocka I Bah MM Korzekwa A Piskula MK Wiczkowski W Depta A Skarzynski DJ 《Experimental biology and medicine (Maywood, N.J.)》2005,230(3):189-199
Phytoestrogens acting as endocrine disruptors may induce various pathologies in the female reproductive tract. The purpose of this study was to determine whether phytoestrogens present in the soybean and/or their metabolites are detectable in the plasma of cows fed a diet rich in soy and whether these phytoestrogens influence reproductive efficiency and prostaglandin (PG) synthesis during the estrous cycle and early pregnancy in the bovine endometrium. In in vivo Experiment 1, we found significant levels of daidzein and genistein in the fodder and their metabolites (equol and p-ethyl-phenol) in bovine serum and urine. The mean number of artificial inseminations (AIs) and pregnancy rates in two kinds of herds, control and experimental (cows fed with soybean 2.5 kg/day), were almost double in the soy-diet herd in comparison with the control animals. In in vivo Experiment 2, three out of five heifers fed soybean (2.5 kg/day) became pregnant whereas four out of five heifers in the control group became pregnant. The concentrations of a metabolite of PGF2alpha (PGFM) were significantly higher in the blood plasma of heifers fed a diet rich in soybean than those in the control heifers throughout the first 21 days after ovulation and AI. The higher levels of PGFM were positively correlated with equol and p-ethyl phenol concentrations in the blood. In in vitro experiments, the influence of isoflavones on PG secretion in different stages of the estrous cycle was studied. Although all phytoestrogens augmented the output of both PGs throughout the estrous cycle, equol and p-ethyl-phenol preferentially stimulated PGF2alpha output. The results obtained lead to the conclusion that soy-derived phytoestrogens and their metabolites disrupt reproductive efficiency and uterus function by modulating the ratio of PGF2alpha to PGE2, which leads to high, nonphysiological production of luteolytic PGF2alpha in cattle during the estrous cycle and early pregnancy. 相似文献