Die Jodierung von Purinnucleosiden

Zusammenfassung Die Jodierung von Guanosin, 2-Deoxyguanosin und Xanthosin wurde untersucht. Es wurde gefunden, daß N-Jodsuccinimid in Dimethylsulfoxid als Lösungsmittel in Gegenwart katalytischer Mengenn-Butyldisulfid als Jodierungsmittel wirkt. Guanosin und Xanthosin geben gute Ausbeuten der 8-Jodverbindungen. Obgleich gewisse Schwierigkeiten in der Jodierung von 2-Deoxyguanosin nicht erklärt werden konnten, ist es möglich, 8-Jod-2-deoxyguanosin in relativ guter Ausbeute zu erhalten.

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The iodination of guanosine, 2-deoxyguanosine and xanthosine has been studied. It was found that N-iodosuccinimide in dimethyl sulfoxide, containingn-butyl disulfide in catalytic amounts, acts as an iodinating agent. Guanosin and xanthosine are readily converted to the 8-iodo compounds. Although certain difficulties in the iodination of 2-deoxyguanosine could not be explained, it is possible to prepare 8-iododeoxyguanosine in fair yield.

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Herrn Prof. Dr.Friedrich Kuffner zum 60. Geburtstag gewidmet.

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Diese Arbeit wurde mit Hilfe von Research Grants der National Science Foundation (NSF-G-12451) und des National Cancer Institute, Public Health Service (CA 03870) durchgeführt.     

Tri-n-butylstannyl-diphenylphosphinoxyd

Ohne Zusammenfassung     

High-temperature reversed-phase liquid chromatography coupled to isotope ratio mass spectrometry

Compound‐specific isotope analysis (CSIA) by liquid chromatography coupled to isotope ratio mass spectrometry (LC/IRMS) has until now been based on ion‐exchange separation. In this work, high‐temperature reversed‐phase liquid chromatography was coupled to, and for the first time carefully evaluated for, isotope ratio mass spectrometry (HT‐LC/IRMS) with four different stationary phases. Under isothermal and temperature gradient conditions, the column bleed of XBridge C₁₈ (up to 180 °C), Acquity C₁₈ (up to 200 °C), Triart C₁₈ (up to 150 °C), and Zirchrom PBD (up to 150 °C) had no influence on the precision and accuracy of δ¹³C measurements, demonstrating the suitability of these columns for HT‐LC/IRMS analysis. Increasing the temperature during the LC/IRMS analysis of caffeine on two C₁₈ columns was observed to result in shortened analysis time. The detection limit of HT‐RPLC/IRMS obtained for caffeine was 30 mg L^–1 (corresponding to 12.4 nmol carbon on‐column). Temperature‐programmed LC/IRMS (i) accomplished complete separation of a mixture of caffeine derivatives and a mixture of phenols and (ii) did not affect the precision and accuracy of δ¹³C measurements compared with flow injection analysis without a column. With temperature‐programmed LC/IRMS, some compounds that coelute at room temperature could be baseline resolved and analyzed for their individual δ¹³C values, leading to an important extension of the application range of CSIA. Copyright © 2011 John Wiley & Sons, Ltd.     

The Alarmone Diadenosine Tetraphosphate as a Cosubstrate for Protein AMPylation

Diadenosine polyphosphates (Ap_nAs) are non-canonical nucleotides whose cellular concentrations increase during stress and are therefore termed alarmones, signaling homeostatic imbalance. Their cellular role is poorly understood. In this work, we assessed Ap_nAs for their usage as cosubstrates for protein AMPylation, a post-translational modification in which adenosine monophosphate (AMP) is transferred to proteins. In humans, AMPylation mediated by the AMPylator FICD with ATP as a cosubstrate is a response to ER stress. Herein, we demonstrate that Ap₄A is proficiently consumed for AMPylation by FICD. By chemical proteomics using a new chemical probe, we identified new potential AMPylation targets. Interestingly, we found that AMPylation targets of FICD may differ depending on the nucleotide cosubstrate. These results may suggest that signaling at elevated Ap₄A levels during cellular stress differs from when Ap₄A is present at low concentrations, allowing response to extracellular cues.