ABSTRACT
Somatic mutations in isocitrate dehydrogenase (IDH)1 and 2 have been identified in a subset of gliomas, rendering these tumors with elevated levels of "oncometabolite," D-2-hydroxyglutarate (2HG). Herein, we report that 2HG can be precisely detected by magnetic resonance (MR) in human glioma specimens and used as a reliable biomarker to identify this subset of tumors. Specifically, we developed a two-dimensional correlation spectroscopy resonance method to reveal the distinctive cross-peak pattern of 2HG in the complex metabolite nuclear MR spectra of brain tumor tissues. This study demonstrates the feasibility, specificity, and selectivity of using MR detection and quantification of 2HG for the diagnosis and classification of IDH1/2 mutation-positive brain tumors. It further opens up the possibility of developing analogous non-invasive MR-based imaging and spectroscopy studies directly in humans in the neuro-oncology clinic.
Subject(s)
Biomarkers, Tumor/metabolism , Brain Neoplasms/metabolism , Glioma/metabolism , Glutarates/metabolism , Isocitrate Dehydrogenase/genetics , Adult , Aged , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Child , Child, Preschool , DNA Mutational Analysis , Female , Glioma/diagnosis , Glioma/genetics , Humans , Magnetic Resonance Spectroscopy/methods , Male , Middle Aged , Sensitivity and Specificity , Young AdultABSTRACT
A new catalyst system for intramolecular olefin aminoacetoxylation is described. In contrast to previously reported palladium- and copper-catalyzed systems, the conditions outlined in this communication favor piperdine formation with terminal olefin substrates and induce cyclization with traditionally less reactive disubstituted olefins.
Subject(s)
Acetone/chemistry , Alkenes/chemistry , Amines/chemistry , Copper/chemistry , Catalysis , Cyclization , Molecular Structure , Oxidation-ReductionABSTRACT
The reactions of chiral benzyl carbocations bearing alpha-phenyl substituents with N-sulfonylated indoles afford 1,1,2-triarylalkanes with anti-selectivities. This outcome is a reversal of facial diastereoselectivity relative to Bach's alpha-alkyl-bearing benzyl cations. The reactions are promoted by either a Brønsted acid (TFA) or Lewis acid (BF3.OEt2), offering differential diastereoselectivities and reactivities. The electronic properties of both reacting partners strongly influence the reaction rates and the product diastereoselectivities and appear to operate under kinetic control. This chemistry provides an efficient access to sterically congested tetrasubstituted ethanes.
Subject(s)
Alkanes/chemical synthesis , Indoles/chemistry , Alkanes/chemistry , Alkylation , Benzene Derivatives/chemistry , Catalysis , Combinatorial Chemistry Techniques , Molecular Structure , StereoisomerismABSTRACT
A new chiroptical spectroscopic approach, differential circularly polarized fluorescence excitation (CPE), can be used to provide a selective method for detecting the presence of zinc ions. The approach utilizes the same instrumentation as fluorescence-detected circular dichroism and provides strong contrast in metal detection due to response to both chelation-enhanced fluorescence and circular dichroism upon metal ion binding. The observed contrast is therefore better than either of the parent spectroscopic detection methods. CPE also provides a strategy to reduce interference from background such as protein-based tryptophan fluorescence.
