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981.
982.
Frank Hannemann Rita Bernhardt Joachim Jose 《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):570-576
Biocatalysis, the conversion of substrates into valuable products by the use of enzymes, has some striking advantages in comparison to standard organic chemistry for drug synthesis. By biocatalysis, substrates that contain several identical reactive groups at different positions can be converted with high regio-selectivity and enantio-selectivity. In this study, an E. coli isolate (E132) was identified which was able to convert the steroid desoxycorticosterone into the product 4-pregnen-20,21-diol-3-one in real terms. The product was purified from the cell culture supernatant by HPLC and its structure was demonstrated by mass spectrometry and NMR spectroscopy. It was tested on inhibition of human 5α-reductases type I and type II. At a concentration of 10 μM, inhibition was 49.0% for type I and 81.8% for type II, whereas there was no inhibition of human aromatase (CYP19) at 20 μM and human 17α-hydroxylase-C17,20-lyase (CYP17) at 2.5 μM detectable. The IC50 value of 4-pregnen-20,21-diol-3-one for human 5α-reductase type II was determined to be 1.56 μM. 相似文献
983.
《Nucleosides, nucleotides & nucleic acids》2013,32(10):1963-1983
Abstract Three chimeric dimer synthons (oeg_tNHT, oeg_upNHT and oeg_uhNHT) containing thymine (t), 5-(l-propynyl)-uracil (up) and 5-(1-hexyn-1-yl)-uracil (uh) PNA units with N-(2-hydroxyethyl)glycine (oeg) backbone were synthesized in solution and incorporated into T20 oligonucleotide analogues, using standard P-amidite chemistry. Insertion of dimer blocks led to destabilization of duplexes with dA20 target. The smallest T m drops were found for chimeras containing oeg_upNHT dimers. Incorporation of the chimeric synthons into the 3′-end of T20 brought about growing resistance to 3′-exonucleolytic (SV PDE) cleavage in the order of oeg_tNHT < oeg_upNHT < oeg_uhNHT. Due to different endonuclease activities of 3′- and 5′-exonucleases applied, placing of five consecutive dimers at the 5′-terminus resulted in a relatively smaller, but also side-chain dependent, stabilization towards the hydrolysis by 5′-exonuclease (BS PDE). Neither exonucleases (SV and BS PDE) nor an endonuclease (Nuclease P1) could hydrolyse the unnatural phosphodiester bond linking the 3′-OH of thymidine to the terminal OH of N-(2-hydroxyethyl)glycine PNA backbone. 相似文献
984.
刘华招 《植物遗传资源学报》2013,14(4):699-703
利用Pi-ta的显性分子标记对寒地稻区水稻骨干亲本合江20号及其衍生品种进行Pi-ta抗性基因传递分析。结果表明,抗病基因Pi-ta在亲本合江20号衍生子一代出现的频率为63%,子二代出现的频率为33%、子三代出现的频率为9%,抗病基因Pi-ta的传递与合江20号衍生系谱一致。抗谱分析表明,Pi-ta抗病基因在子代中出现与衍生品种的抗谱正相关,这可能与后代选择过种中抗病基因的丢失有关,这也可能是决定不同水稻品种的稻瘟病发生程度的主要原因之一。 相似文献
985.
K.P. Silva T.V. SeraphimJ.C. Borges 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(1):351-361
The ubiquitous Hsp90 is critical for protein homeostasis in the cells, stabilizing “client” proteins in a functional state. Hsp90 activity depends on its ability to bind and hydrolyze ATP, involving various conformational changes that are regulated by co-chaperones, posttranslational modifications and small molecules. Compounds like geldanamycin (GA) and radicicol inhibit the Hsp90 ATPase activity by occupying the ATP binding site, which can lead client protein to degradation and also inhibit cell growth and differentiation in protozoan parasites. Our goal was to produce the recombinant Hsp90 of Leishmania braziliensis (LbHsp90) and construct of its N-terminal (LbHsp90N) and N-domain and middle-domain (LbHsp90NM), which lacks the C-terminal dimerization domain, in order to understand how Hsp90 works in protozoa. The recombinant proteins were produced folded as attested by spectroscopy experiments. Hydrodynamic experiments revealed that LbHsp90N and LbHsp90NM behaved as elongated monomers while LbHsp90 is an elongated dimer. All proteins prevented the in vitro citrate synthase and malate dehydrogenase aggregation, attesting that they have chaperone activity, and interacted with adenosine ligands with similar dissociation constants. The LbHsp90 has low ATPase activity (kcat = 0.320 min− 1) in agreement with Hsp90 orthologs, whereas the LbHsp90NM has negligible activity, suggesting the importance of the dimeric protein for this activity. The GA interacts with LbHsp90 and with its domain constructions with different affinities and also inhibits the LbHsp90 ATPase activity with an IC50 of 0.7 μM. All these results shed light on the LbHsp90 activity and are the first step to understanding the Hsp90 molecular chaperone system in L. braziliensis. 相似文献
986.
987.
Yoji Kyotani Hiroyo Ota Asako Itaya-Hironaka Akiyo Yamauchi Sumiyo Sakuramoto-Tsuchida Jing Zhao Kentaro Ozawa Kosuke Nagayama Satoyasu Ito Shin Takasawa Hiroshi Kimura Masayuki Uno Masanori Yoshizumi 《Experimental cell research》2013
Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. 相似文献
988.
989.
Yingke Li Peng Zhang Chengcai Wang Chaofeng Han Jun Meng Xingguang Liu Sheng Xu Nan Li Qingqing Wang Xueyin Shi Xuetao Cao 《The Journal of biological chemistry》2013,288(23):16225-16234
Sepsis-associated immunosuppression (SAIS) is regarded as one of main causes for the death of septic patients at the late stage because of the decreased innate immunity with a more opportunistic infection. LPS-tolerized macrophages, which are re-challenged by LPS after prior exposure to LPS, are regarded as the common model of hypo-responsiveness for SAIS. However, the molecular mechanisms of endotoxin tolerance and SAIS remain to be fully elucidated. In addition, negative regulation of the Toll-like receptor (TLR)-triggered innate inflammatory response needs further investigation. Here we show that expression of immune responsive gene 1 (IRG1) was highly up-regulated in the peripheral blood mononuclear cells of septic patients and in LPS-tolerized mouse macrophages. IRG1 significantly suppressed TLR-triggered production of proinflammatory cytokines TNF-α, IL-6, and IFN-β in LPS-tolerized macrophages, with the elevated expression of reactive oxygen species (ROS) and A20. Moreover, ROS enhanced A20 expression by increasing the H3K4me3 modification of histone on the A20 promoter domain, and supplement of the ROS abrogated the IRG1 knockdown function in breaking endotoxin tolerance by increasing A20 expression. Our results demonstrate that inducible IRG1 promotes endotoxin tolerance by increasing A20 expression through ROS, indicating a new molecular mechanism regulating hypoinflammation of sepsis and endotoxin tolerance. 相似文献
990.
This work is not intended to be a complete review of all publications about entomology in Ecuador. It compiles the history of entomology in Ecuador in a chronological order. It first provides observations about the influence of pre-Columbian cultures and the cultural heritage of indigenous populations. It then presents the contribution of the Spanish conquest and colonization chroniclers, the specialists that described American species during the Renaissance period and the great scientific expeditions. Finally the birth of Ecuadorian entomology as a science is described with the creation of institutes for applied research and the Ecuadorian museums of entomology. 相似文献