共查询到20条相似文献,搜索用时 109 毫秒
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J. Steogon;piński M. Bretner M. Jankowska K. Felczak R. Stolarski Z. Wieczorek 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):717-721
Abstract Chemically synthesized dinucleoside P1, P2-di-, P1, P3-tri- and P1, P4-tetraphosphates, derivatives of 5′-linked 7-methylguanosine and guanosine were characterized with respect to their structural properties and functional effect on eukaryotic translation inhibition. 相似文献
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质量—数量性状遗传参数估计的P1,P2,F1,B1,B2联合分析方法 总被引:2,自引:1,他引:1
提出利用亲本P_1和P_2、杂种F_1、回交B_1和B_1五个世代联合分析包括两个位点主基因控制的质量-数量性状遗传的统计方法,共建立了可供选择的微基因遗传、一对主基因+微基因混合遗传、二对主基因+微基因混合遗传三类五种(套)共 28个遗传模型,采用 AIC信息准则选择最适模型,并通过适合性检验对所选择的遗传模型做进一步的检验.文章最后还讨论了两种变型设计. 相似文献
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Hung Chang Ivan B. Yanachkov Edward J. Dix Milka Yanachkova YouFu Li Marc R. Barnard George E. Wright Alan D. Michelson Andrew L. Frelinger III 《PloS one》2014,9(4)
Background
Diadenosine tetraphosphate (Ap4A), a constituent of platelet dense granules, and its P1,P4-dithio and/or P2,P3-chloromethylene analogs, inhibit adenosine diphosphate (ADP)-induced platelet aggregation. We recently reported that these compounds antagonize both platelet ADP receptors, P2Y1 and P2Y12. The most active of those analogs, diadenosine 5′,5″″-P1,P4-dithio-P2,P3-chloromethylenetetraphosphate, (compound 1), exists as a mixture of 4 stereoisomers.Objective
To separate the stereoisomers of compound 1 and determine their effects on platelet aggregation, platelet P2Y1 and P2Y12 receptor antagonism, and their metabolism in human plasma.Methods
We separated the 4 diastereomers of compound 1 by preparative reversed-phase chromatography, and studied their effect on ADP-induced platelet aggregation, P2Y1-mediated changes in cytosolic Ca2+, P2Y12-mediated changes in VASP phosphorylation, and metabolism in human plasma.Results
The inhibition of ADP-induced human platelet aggregation and human platelet P2Y12 receptor, and stability in human plasma strongly depended on the stereo-configuration of the chiral P1- and P4-phosphorothioate groups, the SPSP diastereomer being the most potent inhibitor and completely resistant to degradation in plasma, and the RPRP diastereomer being the least potent inhibitor and with the lowest plasma stability. The inhibitory activity of SPRP diastereomers depended on the configuration of the pseudo-asymmetric carbon of the P2,P3-chloromethylene group, one of the configurations being significantly more active than the other. Their plasma stability did not differ significantly, being intermediate to that of the SPSP and the RPRP diastereomers.Conclusions
The presently-described stereoisomers have utility for structural, mechanistic, and drug development studies of dual antagonists of platelet P2Y1 and P2Y12 receptors. 相似文献5.
三井东压化学生命科学研究所稻垣明子、该研究所小组负责人藤村达人等使用P_1噬菌体载体编制水稻染色体程序库。农业生物资源研究所染色体研究组已使用酵母人工染色体(YAC)建立了水稻染色体程序库。民间企业独自开发水稻染色体库还是第一次。稻垣等在4月2日~3日召开的日本育种学会和4月1~4日召开的农艺化学会上发表了此项研究成果。 相似文献
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Summary Organic pyrophosphates such as UppA and NAD are formed when a solution containing a nucleotide, a nucleoside 5-polyphosphate, Mg2+ and imidazole are allowed to dry out. We suggest that this synthesis may have occured concurrently with oligonucleotide formation.Abbreviations Im
Imidazole
- CDI
1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride
- EDTA
ethylenediaminetetraacetic acid
- A
adenosine
- U
uridine
- pnA
adenosine 5-poly-phosphate containing n phosphate residues
- pU
uridine 5-phosphate
- AppA
P1,P2-diadenosine 5-pyrophosphate
- UppA
P1-(uridine 5)-P2-(adenosine 5)-pyrophosphate
- ImpA
adenosine 5-phosphorimidazolide
- NMN
nicotinamide mononucleotide
- NAD
nicotinamide-adenine dinucleotide 相似文献
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Abstract A procedure was developed for the chemical synthesis of P1,P2-dinucleoside-5′-diphosphates (N1(5′)pp(5′)N2) on a nanomolar scale Reaction conditions for activating purine-5′-monophosphates (pA, pG, and pm7G) by 1,1′-carbonyldiimidazole were studied and optimized in respect to solvents and amount of activating reagent used. Various dinucleoside-5′-diphosphates were synthesized in 62-98% yield by incubating activated and non-activated purine-5′-monophosphates. Two unexpected by-products were formed by competition reactions: the imidazolidate of the non-activated nucleotide and the corresponding symmetrically substituted dinucleoside-5′-diphosphate. A mechanism is proposed to explain the observed side reactions. 相似文献
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Xu H Zhang H Luan L Xu Y Li C Wang Y Han F Yang T Ren F Xiang JN Elliott JD Zhao Y Guo TB Lu H Zhang W Hirst D Lindon M Lin X 《Bioorganic & medicinal chemistry letters》2012,22(7):2456-2459
High-throughput screening of GSK compound collection led to the discovery of a novel series of thiadiazole amides as potent and S1P(3)-sparing sphingosine-1-phosphate 1 (S1P(1)) receptor agonists. Synthesis, structure and activity relationship, selectivity, and some developability properties are described. 相似文献
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J. Tomasz 《Nucleosides, nucleotides & nucleic acids》2013,32(1):63-79
Abstract The title compound 1 is prepared from thymidine 5′-phos-phorodiamidate (2) and inorganic pyrophosphate (3) in anhydrous DMF, at 30–32°C. The products of alkaline hydrolysis of 1, at room temperature, are: thymidine 5′-phosphoramidate (4), thymidine 3′-phosphoramidate (8) and thymidine (9) as well as 3 and inorganic trimetaphosphate (10). In 1 N NH4OH, 1 reacts with cytidine (15) to form cytidylyl-/2T(3′)-5′/-thymidine (16) and a mixture of cytidine 2′,3′-cyclic phosphate (17) and 9. 相似文献
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用免疫组化技术和PCR-SSCP技术对高、中、低分化大肠腺癌、癌旁粘膜、正常粘膜及大肠腺癌型息肉的P21、P53蛋白表达和k-ras基因、P53基因突变进行检测。结果,大肠腺癌P21、P53蛋白表达比大肠腺瘤增多,但增加不显著(P〉0.05),二组均比癌旁粘膜和正常粘膜P21、P53蛋白表达阳性率高(P〈0.01),大肠腺癌k-ras基因和P53基因突变率比大肠腺瘤、癌旁粘膜和正常粘膜组显著增加 相似文献
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Fujii Y Ueda Y Ohtake H Ono N Takayama T Nakazawa K Igarashi Y Goitsuka R 《Biochemical and biophysical research communications》2012,419(4):754-760
Sphingosine 1-phosphate receptor type 1 (S1P(1)) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P(1) and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P(1)-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P(1) antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P(1) is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies. 相似文献
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目的:研究p57,P53,bcl-2,ki-67蛋白表达在完全性葡萄胎(CM)、部分性葡萄胎(PM)及水肿流产胎(HA)的诊断及鉴别诊断意义.方法:对21例完全性葡萄胎,28例部分性葡萄胎,18例水肿流产胎的标本进行4种抗体免疫组化分析,同时选取10例正常胎盘组织作为对照.结果:在CM中,p57表达不明显,而P53,bcl-2,Ki-67表达增强;在PM,HA及对照组中p57呈现高表达,P53,bcl-2,Ki-67则表达较弱.这四种抗体的表达在完全性葡萄胎与部分性葡萄胎、水肿流产胎及对照组之间的差异具有显著性(P<0.01),而部分性葡萄胎与水肿流产胎、水肿流产胎与对照组之间差异不显著(P>0.05).结论:p57和Ki-67表达对CM,PM和HA的鉴别诊断有重要作用,而P53,bcl-2表达对判断预后及预测恶变风险有意义. 相似文献
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Arun K. Ghosh W. Sean Fyvie Margherita Brindisi Melinda Steffey Johnson Agniswamy Yuan-Fang Wang Manabu Aoki Masayuki Amano Irene T. Weber Hiroaki Mitsuya 《Bioorganic & medicinal chemistry letters》2017,27(21):4925-4931
Design, synthesis, and evaluation of a new class of HIV-1 protease inhibitors containing diverse flexible macrocyclic P1′-P2′ tethers are reported. Inhibitor 5a with a pyrrolidinone-derived macrocycle exhibited favorable enzyme inhibitory and antiviral activity (Ki = 13.2 nM, IC50 = 22 nM). Further incorporation of heteroatoms in the macrocyclic skeleton provided macrocyclic inhibitors 5m and 5o. These compounds showed excellent HIV-1 protease inhibitory (Ki = 62 pM and 14 pM, respectively) and antiviral activity (IC50 = 5.3 nM and 2.0 nM, respectively). Inhibitor 5o also remained highly potent against a DRV-resistant HIV-1 variant. 相似文献
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Asano M Nakamura T Sekiguchi Y Mizuno Y Yamaguchi T Tamaki K Shimozato T Doi-Komuro H Kagari T Tomisato W Inoue R Yuita H Oguchi-Oshima K Kaneko R Nara F Kawase Y Masubuchi N Nakayama S Koga T Namba E Nasu H Nishi T 《Bioorganic & medicinal chemistry letters》2012,22(9):3083-3088
We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P(3)-sparing S1P(1) agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3. Extensive SAR studies led to the finding of 1,3-thiazole 24c with the EC(50) value of 3.4 nM for human S1P(1), and over 5800-fold selectivity against S1P(3). In rat on host versus graft reaction (HvGR), the ID(50) value of 24c was determined at 0.07 mg/kg. The pharmacokinetics in rat and monkey is also reported. Compared to compound 3, 24c showed excellent stability against enterobacteria. 相似文献
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Stephen Hanessian Zhihui Shao Claudia Betschart Jean-Michel Rondeau Ulf Neumann Marina Tintelnot-Blomley 《Bioorganic & medicinal chemistry letters》2010,20(6):1924-1927
Starting from peptidomimetic BACE-1 inhibitors, the P2 amino acid including the P2/P3 peptide bond was replaced by a rigid 3-aminomethyl cyclohexane carboxylic acid. Co-crystallization revealed an unexpected binding mode with the P3/P4 amide bond placed into the S3 pocket resulting in a new hydrogen bond interaction pattern. Further optimization based on this structure resulted in highly potent BACE-1 inhibitors with selectivity over BACE-2 and cathepsin D. 相似文献
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Synthesis of hybrid bisnucleoside 5′, 5‴ — P1, P4 — tetraphosphates by aminoacyl — tRNA synthetases 总被引:2,自引:0,他引:2
Thomas W. Traut 《Molecular and cellular biochemistry》1987,75(1):15-21
Aminoacyl tRNA synthetases, by means of a back reaction, are able to synthesize certain 5, 5 - P1, P4 — bisnucleoside tetraphosphates of biological importance, such as ANA. Here it is shown that HisRS and TrpRS (Bacillus stearothermophilus) and AlaRS (E. coli) also synthesize the hybrid compounds Ap4G, Ap4C, and Ap4U. GInRS (E. coli) is unable to synthesize any of the above compounds.AlaRS synthesizes Ap4U very poorly, and Ap4C and Ap4G almost as effectively as Ap4A. HisRS and TrpRS synthesize Ap4G, Ap4U and Ap3U quite effectively, and Ap4C very poorly. The fact that hybrid bisnucleoside tetraphosphates can be made by the same enzymes, and at rates comparable to Ap4A, suggests that these compounds may also occur in vivo.Abbreviations HPLC
high pressure liquid chromatography
- PEI
polyethyleneimine
- RS
aminoacyl tRNA synthetase 相似文献
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目的:本研究利用酵母三杂交系统从人脑海马回cDNA文库中筛选FXR1P的靶RNA,以进一步阐明FXR1基因的功能。方法:将表达FXR1P全长的质粒pYESTrp3/FXR1转化酵母菌株L40ura3/pHybLex/Zeo-MS2,检测毒性和自激活性;应用酵母三杂交技术从人脑海马回pRH3′-cDNA文库中筛选FXR1P的相互作用RNA;分离初步筛选的结果,再次转化含有诱饵质粒的融合菌株L40ura3/pHybLex/Zeo-MS2/pYESTrp3/FXR1,重新验证阳性结果;最后对阳性结果的外源插入片段进行测序和生物信息学分析。结果:酵母三杂交的筛选得到了3个阳性结果,经过测序和同源性分析,其中一个阳性结果中的插入片段为K-ALPHA-1 mRNA的部分序列。结论:K-ALPHA-1 mRNA可能是一种新的FXR1P的靶RNA。 相似文献