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101.
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Yanyi Wang Jiahua Pu Bolin An Timothy K. Lu Chao Zhong 《Journal of molecular biology》2018,430(20):3720-3734
Many living organisms make use of diverse amyloid proteins as functional building blocks to fulfill a variety of physiological applications. This fact, along with the intrinsic self-assembly and outstanding material properties of amyloids, has prompted a significant amount of research in the synthetic design of functional amyloids to form diverse nanoarchitectures, molecular materials, and hybrid or composite materials. In particular, a new research paradigm has recently been advanced that uses synthetic biology to harness functional amyloids with cells as living materials or functional devices. Here we outline important progress in the synthetic design of functional amyloids, in the context of both non-living and living systems. We propose several important tools and underline emerging techniques and principles that might be useful in advancing the future synthetic design of functional amyloids. 相似文献
103.
Many agents (e.g. camptothecins, indolocarbazoles, indenoisoquinolines, and dibenzonaphthyridines) stimulate topoisomerase I (TOP1)-mediated DNA cleavage (a behavior termed topoisomerase I poisoning) by interacting with both the DNA and the enzyme at the site of cleavage (typically by intercalation between the -1 and +1 base-pairs). The bibenzimidazoles, which include Hoechst 33258 and 33342, are a family of DNA minor groove-directed agents that also stimulate topoisomerase I-mediated DNA cleavage. However, the molecular mechanism by which these ligands poison TOP1 is poorly understood. Toward this goal, we have used a combination of mutational, footprinting, and DNA binding affinity analyses to define the DNA binding site for Hoechst 33258 and a related derivative that results in optimal induction of TOP1-mediated DNA cleavage. We show that this DNA binding site is located downstream from the site of DNA cleavage, encompassing the base-pairs from position +4 to +8. The distal nature of this binding site relative to the site of DNA cleavage suggests that minor groove-directed agents like the bibenzimidazoles poison TOP1 via a mechanism distinct from compounds like the camptothecins, which interact at the site of cleavage. 相似文献
104.
Jizhen Li Ling-Chu Chang Kan-Yen Hsieh Pei-Ling Hsu Stephen J. Capuzzi Ying-Chao Zhang Kang-Po Li Susan L. Morris-Natschke Masuo Goto Kuo-Hsiung Lee 《Bioorganic & medicinal chemistry》2019,27(13):2871-2882
Betulinic acid (BA), a pentacyclic triterpenoid, exhibits broad spectrum antiproliferative activity, but generally with only modest potency. To improve BA’s pharmacological properties, fluorine was introduced as a single atom at C-2, creating two diastereomers, or in a trifluoromethyl group at C-3. We evaluated the impact of these groups on antiproliferative activity against five human tumor cell lines. A racemic 2-F-BA (compound 6) showed significantly improved antiproliferative activity, while each diastereomer exhibited similar effects. We also demonstrated that 2-F-BA is a topoisomerase (Topo) I and IIα dual inhibitor in cell-based and cell-free assays. A hypothetical mode of binding to the Topo I-DNA suggested a difference between the hydrogen bonding of BA and 2-F-BA to DNA, which may account for the difference in bioactivity against Topo I. 相似文献
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Souichi Nukuzuma Chiyoko Nukuzuma Masanori Kameoka Shigeki Sugiura Kazuo Nakamichi Takafumi Tasaki Tsutomu Takegami 《Microbiology and immunology》2017,61(6):232-238
107.
喜树碱诱导的草地贪夜蛾Sf9细胞凋亡 总被引:1,自引:0,他引:1
传统植物源杀虫剂喜树碱具有优异的抑制昆虫生长发育活性, 其诱导昆虫细胞凋亡的作用方式和机制尚不明确, 极大地限制了喜树碱在植物保护领域的应用开发。本研究以1 μmol/L喜树碱诱导草地贪夜蛾Spodoptera frugiperda Sf9细胞呈现细胞皱缩、微绒毛消失和染色质边集等典型细胞凋亡早期超微结构形态特征, 中期凋亡小体逐渐出现并急剧增多, DNA电泳分析可见清晰DNA片段化凋亡特征。流式细胞术分析表明1 μmol/L喜树碱诱导Sf9细胞12 h凋亡率达到最大值39.67%, 是对照的13.13倍, 随后减小。喜树碱诱导Sf9细胞凋亡在12 h和24 h 时Sf caspase-1分别出现两个活性高峰, 表明其作为效应因子在细胞凋亡级联反应过程中具有影响作用。喜树碱显著抑制Sf9细胞拓扑异构酶Ⅰ活性, 阻断解旋负超螺旋pBR322 DNA, 导致DNA损伤进而启动细胞凋亡级联反应使Sf caspase-1活性增加, 提示其信号转导过程是细胞凋亡诱导机制之一。本研究通过分析喜树碱的诱导昆虫Sf9细胞凋亡, 对揭示喜树碱诱导昆虫细胞凋亡的作用机制具有重要启示和帮助。 相似文献
108.
通过组织培养的方法分别对喜树营养器官进行愈伤组织的诱导和继代,筛选红色、黄色和褐色3个不同的细胞系;运用HPLC法测定各愈伤组织中喜树碱的含量,并在培养基中外加诱导子,分析其对愈伤组织中喜树碱含量的影响。结果表明,经幼叶所诱导的愈伤组织中喜树碱含量相对高于其它,红色和黄色的细胞系在不同的外植体中其喜树碱含量均高于褐色的细胞系。但从整体看来,愈伤组织中喜树碱的含量远远低于原植物中的含量。外加诱导子对愈伤组织中喜树碱的含量有影响,浓度为0.1 mg·L-1,1 mg·L-1的水杨酸和茉莉酸甲酯处理的愈伤组织中喜树碱含量提高,0.1 mg·L-1的水杨酸对喜树碱的积累有明显的促进作用,茉莉酸甲酯的影响不大;浓度为3 mg·L-1,5 mg·L-1的水杨酸处理的愈伤组织中,喜树碱含量降低;3 mg·L-1的茉莉酸甲酯处理的愈伤组织中,喜树碱含量降低,5 mg·L-1处理的愈伤组织中未检测到喜树碱。 相似文献
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110.
Cody W. Lewis Ryan G. Taylor Philip M. Kubara Kris Marshall Laurent Meijer Roy M. Golsteyn 《FEBS letters》2013
We developed a quantitative method to measure the activity of cyclin-dependent kinases (Cdks) by western blotting, without radioisotopes. We prepared a recombinant protein substrate based upon the natural Cdk1 substrate, PP1Cα. By combining this substrate in a western blot method using fluorochrome based antibodies and phospho-imager analysis, we measured the Km of ATP binding to Cdk1 to be 3.5 μM. We then measured Cdk1 activity in cell extracts from interphase or mitotic cells, and demonstrated that previously identified Cdk inhibitors could be detected by this assay. Our data show that we have a safe, reliable assay to identify Cdk1 inhibitors and measure Cdk1 activity. 相似文献