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Structurally defined immunostimulatory adjuvants play important roles in the development of new generation vaccines. Here described are the syntheses of three monophosphoryl lipid A analogues (1-3) with different substitution at 3-O-position of the reducing sugar and their potent immunostimulatory adjuvant activity. The syntheses involve the preparation of glycosylation acceptors benzyl 3,4-di-O-benzyl-2-deoxy-2-[(R)-3-tetradecanoyloxytetradecanamido]-beta-D-glucopyranoside (16) and benzyl 3-O-allyl-4-O-benzyl-2-deoxy-2-[(R)-3-tetradecanoyloxytetradecanamido]-beta-D-glucopyranoside (17). The glycosylation reactions between the donor 4,6-di-O-benzylidene-2-deoxy-2-(2',2',2'-trichloroethoxycarbonylamino)-alpha-d-glucopyranosyl trichloroacetimidate (21) and acceptors 16 and 17 provide the desired beta-(1-->6)-linked disaccharides 22 and 23, respectively. Selective reductive ring opening of the 4,6-di-O-benzylidene group, installation of a phosphate group to the 4'-hydroxyl group, and the final global debenzylation produce the designed monophosphoryl lipid A analogues 1-3. All three synthetic analogues induce antigen specific T-cell proliferation and interferon-gamma (IFN-gamma) production in ex vivo experiments with a totally synthetic liposomal vaccine system. The immunostimulatory potency of compound 1-3 is in the same order of magnitude as that of the detoxified natural lipid A product isolated from Salmonella minnesota R595 (R595 lipid A). The substituent at the 3-O-position of the reducing sugar does not have much effect on the adjuvant activity of monophosphoryl lipid A analogues. The preliminary lethal toxicity study indicates that the 3-O-acylated hepta-acyl monophosphoryl lipid A may not be more toxic than its 3-O-deacylated hexa-acyl analogue. 相似文献
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The relationship between alcohol consumption, sensitivity, and tolerance is an important question that has been addressed in humans and rodent models. Studies have shown that alcohol consumption and risk of abuse may correlate with (1) increased sensitivity to the stimulant effects of alcohol, (2) decreased sensitivity to the depressant effects of alcohol, and (3) increased alcohol tolerance. However, many conflicting results have been observed. To complement these studies, we utilized a different organism and approach to analyze the relationship between ethanol consumption and other ethanol responses. Using a set of 20 Drosophila melanogaster mutants that were isolated for altered ethanol sensitivity, we measured ethanol-induced hyperactivity, ethanol sedation, sedation tolerance, and ethanol consumption preference. Ethanol preference showed a strong positive correlation with ethanol tolerance, consistent with some rodent and human studies, but not with ethanol hyperactivity or sedation. No pairwise correlations were observed between ethanol hyperactivity, sedation, and tolerance. The evolutionary conservation of the relationship between tolerance and ethanol consumption in flies, rodents, and humans indicates that there are fundamental biological mechanisms linking specific ethanol responses. 相似文献
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N.K. Damayanthi Ranwala Dennis R. Decoteau Anil P. Ranwala William B. Miller 《Plant Growth Regulation》2002,38(2):157-163
Changes in soluble carbohydrate composition and concentration in leavesand petioles of watermelon (Citrullus lanatus (Thunb)Matsum and Nakai cv. Sugar Baby) seedlings during early stages ofphytochrome-regulated petiole elongation were investigated. Watermelon seedlingswere grown in a controlled environment with 350 molm–2 s–1 photosynthetically activeradiation (PAR) during a 12-h photoperiod. Low intensity end-of-day(EOD) light treatments (for 15 min) of red (R), far-red (FR) and FRfollowed by R (FR/R) were initiated when the seedlings were 14 days old.Seedling growth, and soluble carbohydrate concentration and composition inleaves and petioles were determined after 3 and 6 days of EOD light treatments.The EOD FR increased the petiole length and dry mass partitioned to petioles asearly as 3 days into the treatment. This increased petiole dry mass inFR-treated plants was accompanied with an increase in reducing sugar (glucoseand fructose) concentration in the petioles. Although both leaves and petiolesshowed this effect, the relative increase was greater in petioles than leaves.While the most abundant sugars in petioles were fructose and glucose, thepredominant sugars in leaves were sucrose, raffinose, and stachyose. Thephotoreversion of FR induced changes in growth and sugar concentrations by Rindicates the involvement of phytochrome in these processes. 相似文献
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Michael?WagnerEmail author Dayanand?N?Naik Alex?Pothen Srinivas?Kasukurti Raghu?Ram?Devineni Bao-Ling?Adam O?John?Semmes George?L?WrightJr 《BMC bioinformatics》2004,5(1):26
Background
Recent technological advances in mass spectrometry pose challenges in computational mathematics and statistics to process the mass spectral data into predictive models with clinical and biological significance. We discuss several classification-based approaches to finding protein biomarker candidates using protein profiles obtained via mass spectrometry, and we assess their statistical significance. Our overall goal is to implicate peaks that have a high likelihood of being biologically linked to a given disease state, and thus to narrow the search for biomarker candidates. 相似文献6.
Qin Y Wysocki RJ Somogyi A Feinstein Y Franco JY Tsukamoto T Dunatunga D Levy C Smith S Simpson R Gang D Johnson MA Palanivelu R 《The Plant journal : for cell and molecular biology》2011,68(5):800-815
Polarized cell elongation is triggered by small molecule cues during development of diverse organisms. During plant reproduction, pollen interactions with the stigma result in the polar outgrowth of a pollen tube, which delivers sperm cells to the female gametophyte to effect double fertilization. In many plants, pistils stimulate pollen germination. However, in Arabidopsis, the effect of pistils on pollen germination and the pistil factors that stimulate pollen germination remain poorly characterized. Here, we demonstrate that stigma, style, and ovules in Arabidopsis pistils stimulate pollen germination. We isolated an Arabidopsis pistil extract fraction that stimulates Arabidopsis pollen germination, and employed ultra‐high resolution electrospray ionization (ESI), Fourier‐transform ion cyclotron resonance (FT‐ICR) and MS/MS techniques to accurately determine the mass (202.126 Da) of a compound that is specifically present in this pistil extract fraction. Using the molecular formula (C10H19NOS) and tandem mass spectral fragmentation patterns of the m/z (mass to charge ratio) 202.126 ion, we postulated chemical structures, devised protocols, synthesized N‐methanesulfinyl 1‐ and 2‐azadecalins that are close structural mimics of the m/z 202.126 ion, and showed that they are sufficient to stimulate Arabidopsis pollen germination in vitro (30 μm stimulated approximately 50% germination) and elicit accession‐specific response. Although N‐methanesulfinyl 2‐azadecalin stimulated pollen germination in three species of Lineage I of Brassicaceae, it did not induce a germination response in Sisymbrium irio (Lineage II of Brassicaceae) and tobacco, indicating that activity of the compound is not random. Our results show that Arabidopsis pistils promote germination by producing azadecalin‐like molecules to ensure rapid fertilization by the appropriate pollen. 相似文献
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Animal studies have been instrumental in providing knowledge about the molecular and neural mechanisms underlying drug addiction. Recently, the fruit fly Drosophila melanogaster has become a valuable system to model not only the acute stimulating and sedating effects of drugs but also their more complex rewarding properties. In this review, we describe the advantages of using the fly to study drug-related behavior, provide a brief overview of the behavioral assays used, and review the molecular mechanisms and neural circuits underlying drug-induced behavior in flies. Many of these mechanisms have been validated in mammals, suggesting that the fly is a useful model to understand the mechanisms underlying addiction. 相似文献
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Isyraqiah Faizatul Kutty Methil Kannan Durairajanayagam Damayanthi Singh Harbindar Jeet 《Molecular biology reports》2019,46(6):5967-5975
Molecular Biology Reports - Individuals who are obese are at a greater risk of developing gastric cancer. They are however also hyperleptinaemic. Chronic leptin treatment has been shown to... 相似文献
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Sue Sha Damayanthi Devineni Atalanta Ghosh David Polidori Marcus Hompesch Sabine Arnolds Linda Morrow Heike Spitzer Keith Demarest Paul Rothenberg 《PloS one》2014,9(8)