Primary and secondary alcohols with benzylically and allylically activated C−H bonds are chemoselectively oxidized to the corresponding carbonyl compounds by the (salen)Cr(III) complex I as the ...catalyst and iodosobenzene as the oxygen source; the oxidizing species is the Cr(V) oxo complex. Allylic alcohols with fully substituted double bonds give appreciable amounts of epoxides besides the C−H oxidation products enones, while saturated alcohols are less readily oxidized.
The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been ...corrected in both the PDF and HTML versions of the Article.
Chiral acyclic allylic alcohols 1 have been chemo-, regio-, and diastereoselectively epoxidized to the corresponding epoxy alcohols 2 by catalysis with the achiral manganese(salen) and ...iron(porphyrin) complexes 3 and 4 and iodosyl benzene as oxygen donor. The threo diastereoselectivities establish that hydrogen bonding accounts for the observed hydroxy-group directivity. The dramatically reduced stereoselection in the protic methanol and the opposite sense in the diastereoselectivity (erythro instead of threo) for the ether and ester derivatives 5 of the allylic alcohol 1f confirm that hydrogen bonding between the allylic alcohol and the oxo−metal complex operates in this oxygen-transfer process, with 1,3-allylic strain as the conformationally controlling feature. That metal−alcoholate bonding does not apply is displayed by the regioselectivities obtained in the epoxidation of 1-methylgeraniol (1h). By comparison of the diastereo- and regioselectivities with those of mechanistically defined catalytic and stoichiometric metal and nonmetal oxidants, we propose likely transition-state structures A and B for the present epoxidation.
Zusammenfassung
Therapeutisches Drug-Monitoring (TDM) umfasst die Quantifizierung und die Interpretation von Serum- oder Plasmakonzentrationen von Arzneistoffen im Blut, um die Pharmakotherapie zu ...optimieren. TDM ist ein Werkzeug, mit dem sich die hohe interindividuelle Variabilität der Pharmakokinetik von Patienten identifizieren lässt und es ermöglicht somit eine personalisierte Pharmakotherapie. Im September 2017 veröffentlichte die Arbeitsgruppe Therapeutisches Drug-Monitoring der Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) ein Update der TDM-Konsensusleitlinien. In diesem Artikel sollen die wesentlichen Inhalte für die klinische Praxis in der Psychiatrie und Neurologie zusammengefasst werden.
The activity of mitochondria induces, as a byproduct, a variety of post-translational modifications in associated proteins, which have functional downstream consequences for processes such as ...apoptosis, autophagy, and plasticity; e.g., reactive oxygen species (ROS), which induce N-formyl-kynurenine from oxidized tryptophans in certain mitochondrial proteins which are localized in close spatial proximity to their source. This type of fast molecular changes has profound influence on cell death and survival with implications in a number of pathologies. The quantitative and differential analysis of bovine heart mitochondria by four 2D-PAGE methods, including 2D-PAGE with high-resolution IEF as first dimension, revealed that due to limited resolution, those methods employing blue native-, tricine-urea-, and 16-BAC-PAGE as the first dimension are less applicable for the differential quantitative analysis of redundant protein spots which might give insight into post-translational modifications that are relevant in age- and stress-related changes. Moreover, 2D-PAGE with high resolution IEF was able to resolve a surprisingly large number of membrane proteins from mitochondrial preparations. For aconitase-2, an enzyme playing an important role in mitochondrial aging, a more thorough molecular analysis of all separable isoforms was performed, leading to the identification of two particular N-formylkynurenine modifications. Next to protein redundancy, native protein−protein interactions, with the potential of relating certain post-translational modification patterns to distinct oligomeric states, e.g., oxidative phosphorylation super complexes, might provide novel and (patho-) physiologically relevant information. Among proteins identified, 14 new proteins (GenBank entries), previously not associated with mitochondria, were found. Keywords: mitochondria • proteomics • two-dimensional polyacrylamide gel electrophoresis • IEF-SDS-PAGE • blue native-SDS-PAGE • tricine-urea-SDS-PAGE • 16-BAC-SDS-PAGE • quantitative differential protein expression • membrane proteins • reactive oxygen species • aconitase-2 • N-formylkynurenine • post-translational modifications
Peptide pools are routinely used to study antigen specific T cell responses, both in epitope discovery as well as immune monitoring. However, optimal assay conditions such as concentration of ...peptides or the best possible number of peptides per pool have not been defined. Thus, we examined whether different peptide concentrations or varying number of peptides per pool influence effector functions of antigen-specific human T-cells. PBMC isolated from HLA-A2-positive individuals with known responses to frequently recognised dominant CD8+ T cell epitopes derived from four different viruses (influenza virus, CMV, EBV, or HCV) were studied. PBMC were cultured with one of these HLA-A2 restricted peptides and varying concentrations of overlapping peptide pools derived from unrelated viruses specific for the hepatitis D and E viruses, the subjects have not been exposed to. Importantly, unrelated peptide pools inhibited the proliferation of IV-M158, CMVpp65495–503, EBV-BMLF1259–267 and HCV NS31073-specific CD8 T-cells in a dose dependent manner. Similarly, an increase in the number of peptides per pool also impaired antigen specific CD8+ T cell proliferation. In contrast, secretion of cytokines such as IL-2, IL-10, IFN-gamma, TNF-alpha or IP-10 as well as cytotoxicity was not affected by these unrelated peptide pools. The inhibition of proliferation could be restored by blocking PD-1/PDL-1 interaction and was not dependent on DMSO when DMSO concentration was ≤0.5%.
Thus, peptide-specific CD8 T-cell proliferation but not cytokine production may be largely underestimated when using a peptide pool which warrants caution in immunomonitoring during clinical trials and in epitope discovery studies.
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