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791.
Marco A. Biamonte Jutta Wanner Karine G. Le Roch 《Bioorganic & medicinal chemistry letters》2013,23(10):2829-2843
This digest covers some of the most relevant progress in malaria drug discovery published between 2010 and 2012. There is an urgent need to develop new antimalarial drugs. Such drugs can target the blood stage of the disease to alleviate the symptoms, the liver stage to prevent relapses, and the transmission stage to protect other humans. The pipeline for the blood stage is becoming robust, but this should not be a source of complacency, as the current therapies set a high standard. Drug discovery efforts directed towards the liver and transmission stages are in their infancy but are receiving increasing attention as targeting these stages could be instrumental in eradicating malaria. 相似文献
792.
Nguyen Phuong Thao Le Duc Dat Ninh Thi Ngoc Vu Anh Tu Tran Thi Hong Hanh Phan Thi Thanh Huong Nguyen Xuan Nhiem Bui Huu Tai Nguyen Xuan Cuong Nguyen Hoai Nam Pham Van Cuong Seo Young Yang Sohyun Kim Doobyeong Chae Young-Sang Koh Phan Van Kiem Chau Van Minh Young Ho Kim 《Bioorganic & medicinal chemistry letters》2013,23(6):1823-1827
Three new pyrrole oligoglycosides, astebatheriosides A–C (1–3), and a new furan oligoglycoside, astebatherioside D (4), were isolated from the starfish Asterina batheri by various chromatographic methods. Their structures were elucidated by spectroscopic and chemical methods. Compounds 2, 3, and 4 moderately inhibited IL-12 p40 production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) with IC50 values of 36.4, 31.6, and 22.8 μM, respectively. 相似文献
793.
794.
Angelina M. de Almeida Thiago Nascimento Bianca S. Ferreira Pedro P. de Castro Vânia L. Silva Claúdio G. Diniz Mireille Le Hyaric 《Bioorganic & medicinal chemistry letters》2013,23(10):2883-2887
We report in this work the preparation and in vitro antimicrobial evaluation of novel amphiphilic aromatic amino alcohols synthesized by reductive amination of 4-alkyloxybenzaldehyde with 2-amino-2-hydroxymethyl-propane-1,3-diol. The antibacterial activity was determined against four standard strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa) and 21 clinical isolates of methicillin-resistant Staphylococcus aureus. The antifungal activity was evaluated against four yeast (Candida albicans, Candida tropicalis, Candida glabrata and Candida parapsilosis). The results obtained showed a strong positive correlation between the lipophilicity and the antibiotic activity of the tested compounds. The best activities were obtained against the Gram-positive bacteria (MIC = 2–16 μg ml?1) for the five compounds bearing longer alkyl chains (4c–g; 8–14 carbons), which were also the most active against Candida (MIC = 2–64 μg ml?1). Compound 4e exhibited the highest levels of inhibitory activity (MIC = 2–16 μg ml?1) against clinical isolates of MRSA. A concentration of twice the MIC resulted in bactericidal activity of 4d against 19 of the 21 clinical isolates. 相似文献
795.
Nikolaus E. Schultz Christopher E. Lane Line Le Gall Delphine Gey Anna R. Bigney Bruno De Reviers 《欧洲藻类学杂志》2013,48(4):481-500
In the western Atlantic Ocean, the brown algal genus Lobophora is currently represented by a single species, L. variegata, with a type locality designated by Lamouroux as ‘Antilles’. In this study, we used molecular-assisted alpha taxonomy (MAAT) to assess species diversity of Lobophora in Bermuda, the Florida Keys, St. Croix and Guadeloupe (Lesser Antilles). Using cox1 and cox3 sequences as barcode markers, five species of Lobophora, four of them novel, were delineated, all previously having been identified in the area as L. variegata. Our morphological and habitat studies, made possible by abundant sampling, have revealed unique characters for each of these western Atlantic species, including distinct cellular arrangements, as well as different depth ranges for certain species. Observations made from Lamouroux’s holotype of Dictyota variegata (= Lobophora variegata) allowed us to assess the anatomy of this species, which enabled us to easily align this early taxon to one of our genetic species from the western Atlantic. As the type was unavailable for genetic analysis, we selected a recent St. Croix (Virgin Is., Antilles) specimen as the epitype to support it with molecular sequence data. 相似文献
796.
Chong Li Changyou Zhan Le Zhao Xishan Chen Wei-Yue Lu Wuyuan Lu 《Bioorganic & medicinal chemistry》2013,21(14):4045-4050
Peptide retro-inverso isomerization is thought to be functionally neutral and has been widely used as a tool for designing proteolytically stable d-isomers to recapitulate biological activities of their parent l-peptides. Despite success in a wide range of applications, exceptions amply exist that clearly defy this rule of thumb when parent l-peptides adopt an α-helical conformation in their bound state. The detrimental energetic effect of retro-inverso isomerization of an α-helical l-peptide on its target protein binding has been estimated to be 3.0–3.4 kcal/mol. To better understand how the retro-inverso isomer of a structured protein works at the molecular level, we chemically synthesized and functionally characterized the retro-inverso isomer of a rationally designed miniature protein termed stingin of 18 amino acid residues, which adopts an N-terminal loop and a C-terminal α-helix stabilized by two intra-molecular disulfide bridges. Stingin emulated the transactivation peptide of the p53 tumor suppressor protein and bound with high affinity and via its C-terminal α-helix to MDM2 and MDMX—the two negative regulators of p53. We also prepared the retro isomer and d-enantiomer of stingin for comparative functional studies using fluorescence polarization and surface plasmon resonance techniques. We found that retro-inverso isomerization of l-stingin weakened its MDM2 binding by 720 fold (3.9 kcal/mol); while enantiomerization of l-stingin drastically reduced its binding to MDM2 by three orders of magnitude, sequence reversal completely abolished it. Our findings demonstrate the limitation of peptide retro-inverso isomerization in molecular mimicry and reinforce the notion that the strategy works poorly with biologically active α-helical peptides due to inherent differences at the secondary and tertiary structural levels between an l-peptide and its retro-inverso isomer despite their similar side chain topologies at the primary structural level.1 相似文献
797.
Olivier Demeure Michel J Duclos Nicola Bacciu Guillaume Le Mignon Olivier Filangi Frédérique Pitel Anne Boland Sandrine Lagarrigue Larry A Cogburn Jean Simon Pascale Le Roy Elisabeth Le Bihan-Duval 《遗传、选种与进化》2013,45(1):36
Background
For decades, genetic improvement based on measuring growth and body composition traits has been successfully applied in the production of meat-type chickens. However, this conventional approach is hindered by antagonistic genetic correlations between some traits and the high cost of measuring body composition traits. Marker-assisted selection should overcome these problems by selecting loci that have effects on either one trait only or on more than one trait but with a favorable genetic correlation. In the present study, identification of such loci was done by genotyping an F2 intercross between fat and lean lines divergently selected for abdominal fatness genotyped with a medium-density genetic map (120 microsatellites and 1302 single nucleotide polymorphisms). Genome scan linkage analyses were performed for growth (body weight at 1, 3, 5, and 7 weeks, and shank length and diameter at 9 weeks), body composition at 9 weeks (abdominal fat weight and percentage, breast muscle weight and percentage, and thigh weight and percentage), and for several physiological measurements at 7 weeks in the fasting state, i.e. body temperature and plasma levels of IGF-I, NEFA and glucose. Interval mapping analyses were performed with the QTLMap software, including single-trait analyses with single and multiple QTL on the same chromosome.Results
Sixty-seven QTL were detected, most of which had never been described before. Of these 67 QTL, 47 were detected by single-QTL analyses and 20 by multiple-QTL analyses, which underlines the importance of using different statistical models. Close analysis of the genes located in the defined intervals identified several relevant functional candidates, such as ACACA for abdominal fatness, GHSR and GAS1 for breast muscle weight, DCRX and ASPSCR1 for plasma glucose content, and ChEBP for shank diameter.Conclusions
The medium-density genetic map enabled us to genotype new regions of the chicken genome (including micro-chromosomes) that influenced the traits investigated. With this marker density, confidence intervals were sufficiently small (14 cM on average) to search for candidate genes. Altogether, this new information provides a valuable starting point for the identification of causative genes responsible for important QTL controlling growth, body composition and metabolic traits in the broiler chicken. 相似文献798.
通过18S rDNA基因(SSU)序列,构建了串珠藻目植物的系统发育关系.结果显示:SSU基因序列片段长度为1 871 bp,核苷酸变异位点有709个,占序列长度的38%;其中简约信息位点有169个,占序列长度的9%.用最大似然法、邻接法和贝叶斯法构建的系统树拓扑结构基本一致,都显示红索藻目的2个属独立于串珠藻目成单独分支,支持红索藻目的建立;胶串珠藻独立于其他串珠藻组植物,支持将其单独分组;数据同时支持将扭曲组和杂生组合并,建立Kumanoa属;但多芒组、绿色组、沼生组等因分子序列数据涉及的种类较少,其系统关系的确定还需要更多的证据. 相似文献
799.
目的 探讨表没食子儿茶素没食子酸酯(EGCG)对高脂饮食大鼠脂肪组织中肿瘤坏死因子-α(TNF-α)表达的影响及其与胰岛素敏感性的相关性.方法 将30只SPF级雄性SD大鼠随机分为正常饮食组(ND组,n=10)和高脂饮食组(HFD组,n=20).喂养16w,当两组大鼠体质量出现显著差异后(P〈0.05),将HFD组按随机区组原则分为单纯高脂组(HFD组,n=10)和EGCG干预组(HFD+0.32%EGCG,EGCG组,n=10).干预16w.留取血清及附睾周脂肪组织.检测每组大鼠空腹血糖(FBG)、胰岛素水平(FINS)及游离脂肪酸(FFAs),并计算胰岛素抵抗指数(HOMA-IR);应用Real-time PCR及Western blot方法检测附睾周脂肪组织中TNF-α表达水平.结果 (1)与HFD组相比,EGCG组FINS水平显著下降[分别为(13.83±0.79)mIU/l vs.(31.71±3.61)mIU/l,P〈0.05];HOMA-IR值下降[分别为(3.36±0.31) vs.(7.59±0.99),P〈0.05];FFAs值亦明显下降[分别为(0.38±0.08)mmol/l vs.(0.81±0.11)mmol/l,P〈0.05];三组大鼠FBG水平无明显统计学差异(P〉0.05).(2)与ND组相比,HFD组脂肪组织中TNF-αmRNA水平显著升高[分别为(0.0033±0.00070)vs.(0.0010±0.00008),P〈0.01];而EGCG组较HFD组则明显下降[分别为(0.0018±0.00037)vs.(0.0033±0.00070),P〈0.05];同时,EGCG组TNF-α蛋白表达量低于HFD组[分别为(0.42±0.09)vs.(0.67±0.09),P〈0.05];(3)EGCG组与ND组无明显差异(P〉0.05).结论 EGCG改善高脂饮食大鼠胰岛素敏感性可能与减轻脂肪组织TNF-α介导的炎症状态相关. 相似文献
800.
Dawn Gundersen-Rindal Catherine Dupuy Elisabeth Huguet Jean-Michel Drezen 《Biocontrol Science and Technology》2013,23(1):1-61
One of the more unusual groups of insect pathogens consists of members of the family Polydnaviridae, insect DNA viruses that live in mutual symbioses with their associated parasitoid wasp (Hymentoptera) carriers until they are injected into specific lepidopteran hosts. Once inside this secondary host, polydnaviruses cause a wide variety of negative effects that ultimately ensure the survival of the parasitoid larvae. Because of their unusual life strategy and genetic features, it had been difficult to fully characterise polydnaviruses in terms of evolutionary history, replication cycle and functions in the host that might normally be well characterised for more conventional viruses. Recently, our understanding of polydnavirus evolutionary origins, gene content, genome organisation and functions in parasitism has greatly increased. Key findings are summarised in this review with emphasis on evolution of polydnavirus genes and genomes, their functional roles in insect pathology and their potential applications in insect biological control and biotechnology. 相似文献