Synthesis and biological activity of PTEN-resistant analogues of phosphatidylinositol 3,4,5-trisphosphate

The activation of phosphatidylinositol 3-kinase (PI 3-K) and subsequent production of PtdIns(3,4,5)P3 launches a signal transduction cascade that impinges on a plethora of downstream effects on cell physiology. Control of PI 3-K and PtdIns(3,4,5)P3 levels is an important therapeutic target in treatments for allergy, inflammation, cardiovascular, and malignant human diseases. We designed metabolically stabilized, that is, phosphatase resistant, analogues of PtdIns(3,4,5)P3 as probes for long-lived potential agonists or potential antagonists for cellular events mediated by PtdIns(3,4,5)P3. In particular, two types of analogues were prepared containing phosphomimetics that would be selectively resistant to the lipid 3-phosphatase PTEN. The total asymmetric synthesis of the 3-phosphorothioate-PtdIns(3,4,5)P3 and 3-methylenephosphonate-PtdIns(3,4,5)P3 analogues is described. These two analogues showed differential binding to PtdIns(3,4,5)P3 binding modules, and both were potential long-lived activators that mimicked insulin action in sodium transport in A6 cells.     

Approximate solution of a resource-constrained scheduling problem

This paper is devoted to the approximate solution of a strongly NP-hard resource-constrained scheduling problem which arises in relation to the operability of certain high availability real time distributed systems. We present an algorithm based on the simulated annealing metaheuristic and, building on previous research on exact solution methods, extensive computational results demonstrating its practical ability to produce acceptable solutions, in a precisely defined sense. Additionally, our experiments are in remarkable agreement with certain theoretical properties of our simulated annealing scheme. The paper concludes with a short discussion on further research. This research was supported in part by Association Nationale de la Recherche Technique grant CIFRE-121/2004.     

Optimization of Mn-Mg-Al Mixed Oxides Composition on their Activity towards the Total Oxidation of Aromatic and Oxygenated VOCs

A series of mixed oxides (Mn-Mg-Al) is prepared by coprecipitation via a hydrotalcite route with different manganese ratios. Structural, textural, and redox properties are studied by XRD, N₂-sorption, H₂-TPR, and XPS techniques. Mn_xMg_6-xAl₂-O mixed oxides (with 0≤x≤6) are tested in the total oxidation of ethanol and toluene, two probe molecules representing respectively oxygenated and aromatic VOCs. Catalysts with higher manganese contents have shown the best catalytic performance for the oxidation of both ethanol and toluene. The surface activity of the materials is mainly related to the presence of manganese species in three different oxidation states (+II, +III, and +IV) in the bulk and on the material's surface. Since high Mn-content catalysts showed similar physicochemical properties and catalytic activity, Mn₄Mg₂-O is selected as the optimal composition of these materials. Furthermore, its aging test is compared to that of noble metal-based commercial catalysts (Pd/γ-Al₂O₃).     

Lithiation and Alkylation of the Imidazole Backbone

A concise improved method for the alkylation of the imidazole backbone has been developed. The positions 1 and 2 of the imidazole ring were protected with tetrahydro-2H-pyran-2-yl and chloro groups, respectively. Position 5 of imidazole was then lithiated, whereupon alkylation could be conducted by means of a variety of electrophilic reagents including haloalkanes, aldehydes, and ketones. Finally, the two protective / auxiliary groups on the positions 1 and 2 were easily removed by means of treatment with acid and base and hydrogenation, respectively. The developed method proved good functional group tolerance but demanded non-bulky molecular moieties in the vicinity of the attaching C-atom of the reagent. The novel alkylating method was used to synthesize two new NHC−Ag complexes holding branched alkyl groups on the imidazole backbone.