- Isotope-labeled differential profiling of metabolites using N-benzoyloxysuccinimide derivatization coupled to liquid chromatography/high-resolution tandem mass spectrometry
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Rationale An isotopic labeling strategy based on derivatizing amine-containing metabolites has been developed using light (12C6) and heavy (13C6) N-benzoyloxysuccinimide reagents for semi-targeted metabolomic applications. Methods Differentially labeled samples were combined and analyzed simultaneously by liquid chromatography/high-resolution tandem mass spectrometry (LC/HR-MS/MS) to compare relative amounts of amine-containing metabolites. The selectivity of the reaction was determined with model metabolites and was shown to also be applicable to thiol and phenol moieties. The potential for relative quantitation was evaluated in cell extracts and the method was then applied to quantify metabolic perturbations occurring in human cultured cells under normal vs. oxidative stress conditions. Results A total of 279 derivatized features were detected in HL60 cell extracts, 77 of which yielded significant concentration changes upon oxidative stress treatment. Based on accurate mass measurements and MS/MS spectral matching with reference standard solutions, 10 metabolites were clearly identified. Derivatized compounds were found to have diagnostic fragment ions from the reagent itself, as well as structurally informative ions useful for metabolite identification. Conclusions This simple derivatization reaction can be applied to the relative quantitation of amine-, thiol- and phenol-containing compounds, with improved sensitivity and chromatographic peak shapes due to the increased hydrophobicity of polar metabolites not readily amenable to reversed-phase LC/MS analysis.
- Wagner, Michel,Ohlund, Leanne B.,Shiao, Tze Chieh,Vézina, Amélie,Annabi, Borhane,Roy, René,Sleno, Lekha
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p. 1632 - 1640
(2015/11/16)
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- Synthesis and biological evaluation of 1,3,4-oxadiazoles bearing amino acid moiety
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In the present investigation a series of N-{[5-(4-substituted phenyl)-1,3,4-oxadiazol-2-yl] substituted} benzamide derivatives were synthesized by esterification of 4-substituted aromatic acids followed by hydrazinolysis of esters with hydrazine hydrate to get 4-substituted acid hydrazides. The NH2 group of amino acid was protected using benzoyl chloride. The final step involves the cyclization of acid hydrazides and N-protected amino acid using POCI3 to yield the corresponding N-{[5-(4-substituted phenyl)-1,3,4-oxadiazol-2-yl] substituted} benzamide derivatives. The synthesized compounds were evaluated for antibacterial and antifungal activity. All compounds showed good activity compared to the standard drugs.
- Sankar,Ramajayam
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- Histidine and deuterium labelled histidine by asymmetric catalytic reduction with gaseous H2 or D2; the role of strong non-coordinating acids
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An efficient and convenient route for the preparation of natural and unnatural histidine by asymmetric hydrogenation with rhodium-phosphine complexes is described. The reductions were performed in the presence of HBF4 to generate an essential imidazolyl cation. Stereoselective incorporation of D2 in the α,β-positions was obtained by catalytic deuteration in the presence of MeOD.
- Cesarotti,Rimoldi,Zerla,Aldini
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p. 273 - 278
(2008/09/19)
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