Selective Oxidation of 2′-Deoxyguanosine to Imidazolone by the Chemical Nuclease MnTMPyP Associated to KHSO5 or Sulfite/O2.

Abstract

Mn TMPyP in the presence of sulfite/O₂ catalyses the oxidation of dG into dIz as selectively but slower and less efficiently than in the presence of KHSO_5.     

The use of N-urethane-protected N-carboxyanhydrides (UNCAs) in amino acid and peptide synthesis

N-Urethane-protected N-carboxyanhydrides (UNCAs) are very reactives. They have been successfully used in peptide synthesis, in both solution and solid phase. We have demonstrated that UNCAs are interesting starting materials for the synthesis of various amino acid derivatives. Chemoselective reduction of UNCAs with sodium borohydride led the corresponding N-protected β amino alcohols. Reaction of UNCAs with Meldrum's acid, followed by cyclisation, yielded enantiomerially pure tetramic acid derivatives. Diastereoselective reduction of tetramic acid derivatives produced (4S,5S)-N-alkoxycarbonyl-4-hydroxy-5-alkylpyrrolidin-2-ones derived from amino acids, which after hydrolysis yielded statine and statine analogues. Tetramic acid derivatives could also be obtained by reaction of UNCAs with benzyl ethyl followed by hydrogenolytic deprotection and decarboxylation. UNCAs also reacted with phosphoranes to produce the ketophosphorane in excellent yields. Subsequent oxidation with oxone or with [bis(acetoxy)-iodol]-benzene produced vicinal tricarbonyl derivatives. These reactions usually proceeded smoothly and with high yields.     

Evolutionary study of multigenic families mapping close to the human MHC class I region

Summary During a search for novel coding sequences within the human MHC class I region (chromosome 6p21.3), we found an exon (named B30-2) coding for a 166-amino-acid peptide which is very similar to the C-terminal domain of several coding sequences: human 52-kD Sjögren's syndrome nuclear antigen A/Ro (SS-A/Ro) and ret finger protein (RFP), Xenopus nuclear factor 7 (XNF7), and bovine butyrophilin. The first three of these proteins share similarities over the whole length of the molecule whereas butyrophilin is similar in the C-terminal domain. The N-terminal domain of butyrophilin is similar to rat myelin/oligodendrocyte glycoprotein (MOG) and chicken B blood group system (B-G) protein. These domains are components of a new subfamily of the immunoglobulin superfamily (IgSF). Butyrophilin is thus a mosaic protein composed of the MOG/B-G Ig-like domain and the C-terminal domain of 52-kD SS-A/Ro, RFP, and XNF7 (1330-2-like domain). Moreover, in situ hybridization shows that RFP, butyrophilin, and MOG map to the human chromosome 6p2l.3-6p22 region and are thus close to the MHC class I genes. It is therefore possible that the butyrophilin gene is the product of an exon shuffling event which occurred between ancestors of the RFP and MOG genes. To our knowledge, this is the first example of the colocalization of a chimeric gene and its putative progenitors. Finally, regulatory protein T-lymphocyte 1 (Rpt-1) shares similarities with the N-terminal halves of RFP, 52-kD SS-A/Ro, and XNF7, but not with the B30-2-like domain. We show that the ancestral Rpt-l gene evolved by overprinting. Correspondence to: P. Pontarotti     

Synthesis of Tricyclic Phenylpyrrole Lactams, New Models of Antitubulin Agents

The tricyclic lactams 3 and 4 having a phenylpyrrole framework have been prepared from the arylpyrroles 5 and 16 respectively. These structural analogs of rhazinilam 1 present, like the latter, an interesting antitubulin and cytotoxic activity.     

Simultaneous quantification of cyclophosphamide and its active metabolite 4-hydroxycyclophosphamide in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS)

Cyclophosphamide is a cytotoxic prodrug with a very narrow therapeutic index. To study the clinical pharmacology of cyclophosphamide in a large cohort of patients a previously published method for the simultaneous quantitative determination of cyclophosphamide and 4-hydroxycyclophosphamide in human plasma using liquid chromatography tandem mass spectrometry (LC-MS/MS) was optimized. Addition of an isotopically labelled internal standard and adaptation of the gradient resulted in a fast, robust and sensitive assay. Because 4-hydroxycyclophosphamide is not stable in plasma, the compound is derivatized with semicarbazide immediately after sample collection. Sample preparation was carried out by protein precipitation with methanol-acetonitrile (1:1, v/v), containing isotopically labelled cyclophosphamide and hexamethylphosphoramide as internal standards. The LC separation was performed on a Zorbax Extend C18 column (150 mm x 2.1 mm ID, particle size 5 microm) with 1 mM ammonium hydroxide in water-acetonitrile (90:10, v/v) as the starting gradient, at a flow-rate of 0.40 mL/min with a total run time of 6 min. The lower limit of quantification (LLQ, using a 100 microL sample volume) was 200 ng/mL and the linear dynamic range extended to 40,000 ng/mL for cyclophosphamide and 50-5000 ng/mL for 4-hydroxycyclophosphamide. Accuracies as well as precisions were lower than 20% at the LLQ concentration and lower than 15% for all other concentrations. This method has been successfully applied in our institute to support ongoing studies into the pharmacokinetics and pharmacogenetics of cyclophosphamide.     

Contrasting effects of N and P deprivation on the regulation of photosynthesis in tomato plants in relation to feedback limitation

The effects were studied of both nitrogen and phosphorus limitation and irradiance on the performance and operation of photosynthesis in tomato leaves (Lycopersicon esculentum Mill.). Plants were grown at low N, high N, low P or high P supply and at two irradiances. Using mature leaves, measurements were made of the irradiance dependencies of the relative quantum efficiencies of photosystems I and II, and of the rate of carbon dioxide fixation. Measurements were also made of foliar starch and chlorophyll concentrations. The results showed that photosynthetic light-harvesting and electron-transport activity acclimate to nutrient stress and growth irradiance such that the internal relationships between electron transport by photosystems I and II do not change; the linear relationship between PhiPSII, and PhiPSI was not affected. It was also evident that under N stress photosynthesis was reduced by a decreased light absorption and by the decreased utilization of assimilates, while P stress mainly affected the carboxylation capacity. Under N stress foliar starch levels increased and the oxygen sensitivity of CO2 fixation decreased, whereas P stress resulted in decreased starch levels and increased oxygen sensitivity of CO2 fixation. The relationship between starch accumulation and oxygen sensitivity (increased starch correlated with decreased oxygen sensitivity) was always the same across the nutrient treatments. These results are consistent with N deprivation producing an increasing limitation of photosynthesis, possibly by feedback from the leaf carbohydrate pool, whereas, although P deprivation produces a decreased rate of CO2 fixation, this is accompanied by a increase in oxygen sensitivity, suggesting that feedback limitation is decreased under P stress.