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151.
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153.
Luo G Chen L Civiello R Pin SS Xu C Kostich W Kelley M Conway CM Macor JE Dubowchik GM 《Bioorganic & medicinal chemistry letters》2012,22(8):2917-2921
In our continuing efforts to identify CGRP receptor antagonists that can be dosed orally for the treatment of migraine headache, we have investigated a pyridine bioisosteric replacement of a polar amide portion of a previous lead compound, BMS-694153. Pyridine derivatives were discovered and their SAR was studied. Some of them showed excellent binding potency. However, oral bioavailability was low, even for compounds with good Caco-2 cell permeability. 相似文献
154.
利用温室盆栽试验,研究了不同光强100%、40%、20%和5%下三叶鬼针草营养生长期和繁殖期的生长特征。结果表明:中度遮荫有利于三叶鬼针草支持结构的生长和营养期的物质积累,重度遮荫下仍能生长良好。在两个生长时期,相对生长速率(RGR)、净同化速率(NAR)均在100%光强下最大,5%光强下最小;总生物量在营养期和繁殖期分别在40%光强和全光照下最大,在3%光强下最小;株高、总叶面积(TLA)、根生物量比(RMR)、根冠比(R/C)、叶生物量比(LMR)、比叶面积(SLA)、叶面积比(LAR)、平均叶面积比(LARm)在3%光强时均大于全光照下的;支持结构生物量比(SBR)在40%光强、20%光强下大于3%光强和全光照处理。这说明三叶鬼针草在形态、生物量分配及生长特性上对光因素具较强的可塑性,这可能是其分布范围广、具有强入侵性的因素之一。 相似文献
155.
血管活性肠肽对脓毒性休克大鼠肝损伤的保护作用 总被引:1,自引:0,他引:1
采用盲肠结扎穿孔(cecal ligation and puncture,CLP)法制备脓毒性休克大鼠模型,探讨血管活性肠肽(vasoactive intestinal peptide,VIP)对脓毒性休克大鼠肝损伤的保护作用及其可能机制.将48只雄性SD大鼠随机分成4组:假手术组(SO,n=12)、CLP组(n=12)、VIP组(n=12)和生理盐水组(NS,n=12).VIP组大鼠在行CLP术后即刻给予6 nmol VIP,应用酶联免疫吸附试验(ELISA)检测各组大鼠血清谷丙转氨酶ALT和谷草转氨酶AST水平,同时检测血清炎症因子:促炎因子肿瘤坏死因子-α(TNF-α),抑炎因子白介素-10(IL-10)的变化;取大鼠肝脏组织行病理检查.在6 h以后的各时间点,与NS组比较,VIP组TNF-α水平明显降低,IL-10水平持续升高,VIP组AST和ALT水平自12 h始明显降低,肝脏病理损伤明显改善.实验表明,VIP通过抑制促炎因子的生成并促进抗炎因子的产生在大鼠脓毒性休克肝损伤中发挥保护作用. 相似文献
156.
Human beta-defensin-2 (hBD2) is A small cationic peptide with A broad range of antimicrobial activity. An E. coli cell-free system was employed to express the hBD2 fusion protein by using the hBD2 gene with 14 rare codons. The results showed that the expression level of trxA-hBD2 fusion protein was 0.35 mg/ml, which is the same as that obtained with A synthetic codon-optimized gene. By using another fusion partner (GFP), similar high-level expression was also achieved in this cell-free system. This meant that human beta-defensin-2 gene could be directly used to express hBD2 fusion protein efficiently in an E. coli cell-free system without the optimization of codons. The expression level of hBD2 fused with thioredoxin could be further improved up to 2.0 mg/ml by adopting A continuous exchange cell-free system. A simple one-stage affinity purification procedure was also developed to recover this fusion protein efficiently. 相似文献
157.
Zhihua Jin Yinlin Lei Jianping Lin Peilin Cen 《World journal of microbiology & biotechnology》2006,22(2):129-134
Summary According to the biosynthetic pathway of pristinamycin, a rational selection procedure with u.v. mutation was performed to obtain a high pristinamycin-producing strain. Aminoacetic acid-resistant mutants (AAr), valine hydroxamate-resistant mutants (VHr), kitasamycin-resistant mutants (KTMr) and 2-deoxy-D-glucose-resistant mutants (DOGr) were selected, successively. A strain Streptomyces pristinaespiralis 12–55 with AAr, Valr, KTMr, and DOGr was obtained, and its production of pristinamycin reached 3000 u/ml which is 100 times higher than that of the parent strain S. pristinaespiralis ATCC 25486. It is inferred that S. pristinaespiralis 12–55 can alleviate catabolite repression caused by carbon sources, provide more acetic acid and valine for pristinamycin biosynthesis and increase its resistance to pristinamycin produced by itself, all of which are favorable for pristinamycin production. The subculture experiments indicated that the hereditary character of high productivity of S. pristinaespiralis 12–55 is stable. The pristinamycin production of S. pristinaespiralis 12–55 in a 15-l fermentor could reach 3010 u/ml after a 56 h batch fermentation. 相似文献
158.
Xiyang Chen Peilian Wei Limei Fan Dong Yang Xiangchen Zhu Wenhe Shen Zhinan Xu Peilin Cen 《Applied microbiology and biotechnology》2009,83(3):507-512
Rapamycin is a 31-member ring macrolide produced by Streptomyces hygroscopicus and has many applications in clinical medicine. In the present work, several protoplasts-related techniques including protoplasts
mutation, intraspecies and interspecies protoplasts fusion were tried to improve the rapamycin productivity in S. hygroscopicus. Although mutation and fusion of different protoplasts of S. hygroscopicus did not improve the productivity of rapamycin significantly, the interspecies fusion of protoplasts of S. hygroscopicus D7-804 and Streptomyces erythreus ZJU325 could have brought about one high-yield (345 mg/L) rapamycin producer with 23.6% higher than that of the parental
strain. Then, with seven mutants of S. hygroscopicus with different features and rapamycin productivities as the parental strains, only one-round genome shuffling has generated
a high-yield rapamycin-producing strain with an outstanding yield of 445 mg/L. The systematic research of protoplast-related
techniques has established an applicable way to generate high-yield strains from original microorganisms which can only produce
low amount of expected natural products, without information of target gene clusters and gene sequences. 相似文献
159.
滇黄芩器官发生与不同继代次数遗传稳定性的RAPD分析 总被引:2,自引:0,他引:2
本研究以滇黄芩不带腋芽茎段为外植体,采用不同配比激素的MS培养基建立了滇黄芩器官发生,植株再生体系.结果表明,茎段在MS+6-BA 2 mg/L+NAA 0.5 mg/L培养基上培养时,愈伤组织诱导率达到100%:以相同培养基进行分化,并在MS+6-BA 2 mg/L+NAA 0.2 mg/L培养基上扩繁丛生芽.在1/2MS+IBA 0.2 mg/L培养基诱导生根,扦插继代.利用RAPD分析不同继代次数再生植株,所用的39条随机引物中只有1条引物带型发生变化.说明经组织培养获得的再生植株遗传稳定,可多次继代培养,为滇黄芩进一步遗传操作和扩大药材资源奠定基础. 相似文献
160.