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151.
Nigel Greene Michael D. Aleo Shirley Louise-May David A. Price Yvonne Will 《Bioorganic & medicinal chemistry letters》2010,20(17):5308-5312
Recent publications have demonstrated that using calculated physiochemical properties can help in the design of compounds that have a decreased risk of significant findings in rodent toxicology studies. In this Letter, we extend this concept and incorporate results from a high throughput cytotoxicity assay to help the drug discovery community select compounds for progression into in vivo studies. The results are presented in an easily interpretable odds ratio so that teams can readily compare compounds and progress potential clinical candidates to the necessary rodent in vivo studies. 相似文献
152.
Kerstin Sander Yvonne von Coburg Jean-Claude Camelin Xavier Ligneau Oliver Rau Manfred Schubert-Zsilavecz Jean-Charles Schwartz Holger Stark 《Bioorganic & medicinal chemistry letters》2010,20(5):1581-1584
Antagonists of the human histamine H3 receptor (hH3R) often contain a second basic moiety, which is well known to boost affinity on this histamine receptor subtype. Here, we prepared compounds with acidic moieties of different pKa values to figure out that the hH3R tolerates these functionalities when added to a common pharmacophore blueprint. Depending on the acidic, electronic and steric features the designed ligands showed hH3R affinities in the nanomolar concentration range. Additionally, selected ligands were tested but failed as dual acting hH3R/hPPAR (human peroxisome proliferator-activated receptor) ligands. 相似文献
153.
154.
Yvonne Meyer-Lucht Celine Otten Thomas Püttker Renata Pardini Jean Paul Metzger Simone Sommer 《Conservation Genetics》2010,11(5):2001-2013
The adaptive potential of a species to a changing environment and in disease defence is primarily based on genetic variation.
Immune genes, such as genes of the major histocompatibility complex (MHC), may thereby be of particular importance. In marsupials,
however, there is very little knowledge about natural levels and functional importance of MHC polymorphism, despite their
key role in the mammalian evolution. In a previous study, we discovered remarkable differences in the MHC class II diversity
between two species of mouse opossums (Gracilinanus microtarsus, Marmosops incanus) from the Brazilian Atlantic forest, which is one of the most endangered hotspots for biodiversity conservation. Since the
main forces in generating MHC diversity are assumed to be pathogens, we investigated in this study gastrointestinal parasite
burden and functional associations between the individual MHC constitution and parasite load. We tested two contrasting scenarios,
which might explain differences in MHC diversity between species. We predicted that a species with low MHC diversity would
either be under relaxed selection pressure by low parasite diversity (‘Evolutionary equilibrium’ scenario), or there was a recent loss in MHC diversity leading to a lack of resistance alleles and increased parasite burden
(‘Unbalanced situation’ scenario). In both species it became apparent that the MHC class II is functionally important in defence against gastrointestinal
helminths, which was shown here for the first time in marsupials. On the population level, parasite diversity did not markedly
differ between the two host species. However, we did observe considerable differences in the individual parasite load (parasite
prevalence and infection intensity): while M. incanus revealed low MHC DAB diversity and high parasite load, G. microtarsus showed a tenfold higher population wide MHC DAB diversity and lower parasite burden. These results support the second scenario
of an unbalanced situation. 相似文献
155.
Announcement
Call for papers: Symposium on “Tautomers and biology,” American Chemical Society National Meeting, Boston, MA, USA, August 2010 相似文献156.
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158.
159.
Background
Fine tuning expression of genes is a prerequisite for the strictly human pathogen Neisseria meningitidis to survive hostile growth conditions and establish disease. Many bacterial species respond to stress by using alternative σ factors which, in complex with RNA polymerase holoenzyme, recognize specific promoter determinants. σE, encoded by rpoE (NMB2144) in meningococci, is known to be essential in mounting responses to environmental challenges in many pathogens. Here we identified genes belonging to the σE regulon of meningococci. 相似文献160.