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Vanessa Gouge-Ibert Camille Pierry Florent Poulain Anne-Lise Serre Céline Largeau Virginie Escriou Daniel Scherman Philippe Jubault Jean-Charles Quirion Eric Leclerc 《Bioorganic & medicinal chemistry letters》2010,20(6):1957-1960
The synthesis of fluorinated C-mannopeptides and their evaluation as E- and P-selectin inhibitors is described. These molecules are difluorinated analogues of CH2-glycopeptides already reported to act as sLex mimics. The α and β anomers of these CF2-glycopeptides have been prepared, as well as their 1-hydroxy analogues which were present in solution as an equilibrium mixture of α- and β-pyranose and α- and β-furanose forms. These molecules showed inhibitory activities comparable to their CH2 counterparts with a moderate influence of the pseudo-anomeric center configuration. 相似文献
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Michael Carland Murray J. Cairns Vanessa J. Roknic W. David McFadyen 《Journal of inorganic biochemistry》2010,104(8):815-819
Three platinum complexes in which substituted (7-OMe, 9-NH2; 7-F, 9-NH2; and 7-H, 9-NH(CH2)2OH) 9-aminoacridine-4-carboxamides were tethered to a platinum(II)diamine moiety were synthesised and characterised at the chemical and biological level. These variants showed a decrease in cytotoxicity, as measured by IC50 values in HeLa cells, when compared with the parent 7-H, 9-NH2 compound. The 7-F and 9-NH(CH2)2OH substituents gave rise to a small decrease in cytotoxicity, and the 7-OMe substituent resulted in a larger decrease in cytotoxicity. Their binding to purified pUC19 plasmid DNA was investigated and it was found that the addition of 7-F, 9-NH(CH2)2OH and especially the 7-OMe substituents, resulted in reduced DNA binding. This correlated well with the IC50 cytotoxicity values. However, the DNA sequence selectivity was unaffected by the addition of these moieties. 相似文献
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The subjective value of a reward (gain) is related to factors such as its size, the delay to its receipt and the probability of its receipt. We examined whether the subjective value of losses was similarly affected by these factors in 128 adults. Participants chose between immediate/certain gains or losses and larger delayed/probabilistic gains or losses. Rewards of $100 were devalued as a function of their delay (“discounted”) relatively less than $10 gains while probabilistic $100 rewards were discounted relatively more than $10 rewards. However, there was no effect of outcome size on discounting of delayed or probabilistic losses. For delayed outcomes of each size, the degree to which gains were discounted was positively correlated with the degree to which losses were discounted, whereas for probabilistic outcomes, no such correlation was observed. These results suggest that the processes underlying the subjective valuation of losses are different from those underlying the subjective valuation of gains. 相似文献
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Mervyn Beukes Yolandy Lemmer Madrey Deysel Juma’a R. Al Dulayymi Mark S. Baird Gani Koza Maximiliano M. Iglesias Richard R. Rowles Cornelia Theunissen Johan Grooten Gianna Toschi Vanessa V. Roberts Lynne Pilcher Sandra Van Wyngaardt Nsovo Mathebula Mohammed Balogun Anton C. Stoltz Jan A. Verschoor 《Chemistry and physics of lipids》2010,163(8):800-808
Cell wall mycolic acids (MA) from Mycobacterium tuberculosis (M.tb) are CD1b presented antigens that can be used to detect antibodies as surrogate markers of active TB, even in HIV coinfected patients. The use of the complex mixtures of natural MA is complicated by an apparent antibody cross-reactivity with cholesterol. Here firstly we report three recombinant monoclonal scFv antibody fragments in the chicken germ-line antibody repertoire, which demonstrate the possibilities for cross-reactivity: the first recognized both cholesterol and mycolic acids, the second mycolic acids but not cholesterol, and the third cholesterol but not mycolic acids. Secondly, MA structure is experimentally interrogated to try to understand the cross-reactivity. Unique synthetic mycolic acids representative of the three main functional classes show varying antigenicity against human TB patient sera, depending on the functional groups present and on their stereochemistry. Oxygenated (methoxy- and keto-) mycolic acid was found to be more antigenic than alpha-mycolic acids. Synthetic methoxy-mycolic acids were the most antigenic, one containing a trans-cyclopropane apparently being somewhat more antigenic than the natural mixture. Trans-cyclopropane-containing keto- and hydroxy-mycolic acids were also found to be the most antigenic among each of these classes. However, none of the individual synthetic mycolic acids significantly and reproducibly distinguished the pooled serum of TB positive patients from that of TB negative patients better than the natural mixture of MA. This argues against the potential to improve the specificity of serodiagnosis of TB with a defined single synthetic mycolic acid antigen from this set, although sensitivity may be facilitated by using a synthetic methoxy-mycolic acid. 相似文献
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Indirect chilling injury commonly occurs during long-term exposure to low temperature in many organisms including insects. A previous study revealed increased rates of survival and reduced cold injury in flesh flies, Sarcophaga crassipalpis, that experienced an intermittent pulse of high temperature during a low-temperature regiment. We extended these studies by determining survival rates and ATP levels for flies that had undergone continuous long-term exposure at 0 °C versus those experiencing a 24-h warming pulse of either 15 or 20 °C. Survival among flies that had undergone a warming pulse was significantly greater than for flies that were maintained continuously at 0 °C. Furthermore, ATP levels of flies that had experienced a warming pulse were significantly higher than those of flies maintained at 0 °C. These data suggest that brief warming pulses during long-term cold storage allow regeneration of energy reserves that promote survival and reduce indirect chilling injury. 相似文献