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111.
O'Neill PM Verissimo E Ward SA Davies J Korshin EE Araujo N Pugh MD Cristiano ML Stocks PA Bachi MD 《Bioorganic & medicinal chemistry letters》2006,16(11):2991-2995
A Diels-Alder/thiol-olefin co-oxygenation approach to the synthesis of novel bicyclic endoperoxides 17a-22b is reported. Some of these endoperoxides (e.g., 17b, 19b, 22a and 22b) have potent nanomolar in vitro antimalarial activity equivalent to that of the synthetic antimalarial agent arteflene. Iron(II)-mediated degradation of sulfone-endoperoxide 19b and spin-trapping with TEMPO provide a spin-trapped adduct 25 indicative of the formation of a secondary carbon centered radical species 24. Reactive C-radical intermediates of this type may be involved in the expression of the antimalarial effect of these bicyclic endoperoxides. 相似文献
112.
Umberto Restuccia Egisto Boschetti Elisa Fasoli Frederic Fortis Luc Guerrier Angela Bachi Alexander V. Kravchuk Pier Giorgio Righetti 《Journal of Proteomics》2009,72(6):1061
The pre-treatment of biological extracts with the aim of detecting very low-abundance proteins generates complexity requiring a proper fractionation. Therefore the success of identifying all newly detectable species depends on the selected fractionation methods.In this context and starting from a human serum, where the dynamic concentration range was reduced by means of a preliminary treatment with a combinatorial hexapeptide ligand library, we fractionated the sample using a novel method based on the differences in isoelectric points of proteins by means of Solid-State Buffers (SSB) associated with cation exchangers. The number of fractions was limited to four and was compared to a classical anion exchange method generating the same number of fractions.What was observed is that when using SSB technology the protein redundancy between fractions was significantly reduced compared to ion exchange fractionation allowing thus a better detection of novel species. The analysis of trypsinized protein fractions by nanoLC-MS/MS confirmed that the SSB technology used is more discriminant than anion exchange chromatography fractionation.A sample fractionation by SSB after the reduction of dynamic concentration range can be accomplished without either adjustment of pH and ionic strength or protein concentration and cleanup. Both advantages over either classical chromatography or isoelectric fractionations allow approaching the discovery of markers of interest under easier conditions applicable in a variety of fields of investigation. 相似文献
113.
114.
Flavio Curnis Angela Cattaneo Renato Longhi Angelina Sacchi Anna Maria Gasparri Fabio Pastorino Paola Di Matteo Catia Traversari Angela Bachi Mirco Ponzoni Gian-Paolo Rizzardi Angelo Corti 《The Journal of biological chemistry》2010,285(12):9114-9123
Various NGR-containing peptides have been exploited for targeted delivery of drugs to CD13-positive tumor neovasculature. Recent studies have shown that compounds containing this motif can rapidly deamidate and generate isoaspartate-glycine-arginine (isoDGR), a ligand of αvβ3-integrin that can be also exploited for drug delivery to tumors. We have investigated the role of NGR and isoDGR peptide scaffolds on their biochemical and biological properties. Peptides containing the cyclic CNGRC sequence could bind CD13-positive endothelial cells more efficiently than those containing linear GNGRG. Peptide degradation studies showed that cyclic peptides mostly undergo NGR-to-isoDGR transition and CD13/integrin switching, whereas linear peptides mainly undergo degradation reactions involving the α-amino group, which generate non-functional six/seven-membered ring compounds, unable to bind αvβ3, and small amount of isoDGR. Structure-activity studies showed that cyclic isoDGR could bind αvβ3 with an affinity >100-fold higher than that of linear isoDGR and inhibited endothelial cell adhesion and tumor growth more efficiently. Cyclic isoDGR could also bind other integrins (αvβ5, αvβ6, αvβ8, and α5β1), although with 10–100-fold lower affinity. Peptide linearization caused loss of affinity for all integrins and loss of specificity, whereas α-amino group acetylation increased the affinity for all tested integrins, but caused loss of specificity. These results highlight the critical role of molecular scaffold on the biological properties of NGR/isoDGR peptides. These findings may have important implications for the design and development of anticancer drugs or tumor neovasculature-imaging compounds, and for the potential function of different NGR/isoDGR sites in natural proteins. 相似文献
115.
Alfonsina D'Amato Alexander V. Kravchuk Angela Bachi Pier Giorgio Righetti 《Journal of Proteomics》2010,73(12):2370-2377
Combinatorial peptide ligand libraries (CPLLs) have been adopted for harvesting and identifying traces of proteins present in red wines. Surprisingly, although it is stated that red wines are in general fined with egg albumin, for all Italian wines investigated (in the areas around Chiari and Verona as well as in the Chianti area) we find that the only fining agent used is bovine casein, just like in white wines. Although the typical levels of casein found range between 45 to 85 μg/L, in one case as little as 3.8 μg/L of casein could be detected, an extremely high level of sensitivity, close to our lower detection limit of 1 μg/L reported for white wines. As a result of such treatments, very small amounts of residual proteins in red wines could be identified: essentially no residual grape proteins (except for thaumatin), but only traces of proteins from Saccharomyces cerevisiae and a few proteins from plant pathogens and fungi (e.g., Botryotinia fuckeliana, Sclerotinia sclerotiorum, Aspergillus aculeatus). Contrary to what has been found in white wines, the best capture efficiency with CPLLs has occurred at pH 7.2 and pH 9.3, with minimal capture at pH 3.3. The fact that such very low levels of fining agents can still be detected in treated red wines should be taken into consideration by winemakers in labelling their products and by EC rulers in issuing proper regulations. 相似文献
116.
117.
The Stomach, Helicobacter pylori, and Acid Secretion 总被引:1,自引:0,他引:1
118.
Dorsey DA Mascó DH Dikranian K Hyrc K Masciotra L Faddis B Soriano M Gru AA Goldberg MP de Erausquin GA 《Apoptosis : an international journal on programmed cell death》2006,11(4):535-544
Developing neuronal populations undergo significant attrition by natural cell death. Dopaminergic neurons in the substantia
nigra pars compacta undergo apoptosis during synaptogenesis. Following this time window, destruction of the anatomic target
of dopaminergic neurons results in dopaminergic cell death but the morphology is no longer apoptotic. We describe ultrastructural
changes that appear unique to dying embryonic dopaminergic neurons. In primary cultures of mesencephalon, death of dopaminergic
neurons is triggered by activation of glutamate receptors sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid (AMPA), and differs ultrastructurally from both neuronal apoptosis or typical excitotoxicity. AMPA causes morphological
changes selectively in dopaminergic neurons, without affecting other neurons in the same culture dishes. Two hours after the
onset of treatment swelling of Golgi complexes is apparent. At 3 h, dopaminergic neurons display loss of membrane asymmetry
(coinciding with commitment to die), as well as nuclear membrane invagination, irregular aggregation of chromatin, and mitochondrial
swelling. Nuclear changes continue to worsen until loss of cytoplasmic structures and cell death begins to occur after 12 h.
These changes are different from those described in neurons undergoing either apoptosis or excitotoxic death, but are similar
to ultrastructural changes observed in spontaneous death of dopaminergic neurons in the natural mutant weaver mouse. 相似文献
119.
Schrotz-King P Wilm M Andersen JS Ashman K Podtelejnikov AV Bachi A King A Mann M 《Journal of receptor and signal transduction research》1999,19(1-4):659-672
In recent years, mass spectrometry has become the method of choice for identifying small amounts of gel separated proteins. Using high mass accuracy peptide mass mapping followed if necessary by nanoelectrospray sequencing, most mammalian proteins can now be identified quickly and sensitively either in amino acid or in EST sequence databases. These methods are illustrated here using an ongoing project in the author's laboratory, a mass spectrometric screen for new mouse brain receptors and their interaction partners. 相似文献
120.
Ortega A Niksic M Bachi A Wilm M Sánchez L Hastie N Valcárcel J 《The Journal of biological chemistry》2003,278(5):3040-3047
Genetic and molecular data have implicated the Drosophila gene female-lethal (2)d (fl (2)d) in alternative splicing regulation of genes involved in sexual determination. Sex-specific splicing is under the control of the female-specific regulatory protein sex-lethal (SXL). Co-immunoprecipitation and mass spectrometry results indicate that SXL and FL (2)D form a complex and that the protein VIRILIZER and a Ran-binding protein implicated in protein nuclear import are also present in complexes containing FL (2)D. A human homolog of FL (2)D was identified and cloned. Interestingly, this gene encodes a protein (WTAP) that was previously found to interact with the Wilms' tumor suppressor-1 (WT1), an isoform of which binds to and co-localizes with splicing factors. Alternative splicing of transformer pre-mRNA, a target of SXL regulation, was affected by immunodepletion of hFL (2)D/WTAP from HeLa nuclear extracts, thus arguing for a biochemical function of FL (2)D/WTAP proteins in splicing regulation. 相似文献