Direct glucosone-based synthesis and HILIC-ESI-MS/MS characterization of N-terminal fructosylated valine and valylhistidine for validation of enzymatic HbA1c assays in the diagnosis of diabetes mellitus

Autor:	Reinhard Meusinger, Matthias Grimmler, Erwin Metzmann, Monika Buchholz, Christoph Gerke, Holger Müller
Rok vydání:	2019
Předmět:	Spectrometry Mass Electrospray Ionization Electrospray ionization Fructose 010402 general chemistry 01 natural sciences Biochemistry Reductive amination Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound Diabetes mellitus Tandem Mass Spectrometry Valine Ketoses Fructosamines Humans Histidine HbA1c quantification Paper in Forefront Enzyme Assays 030304 developmental biology Glycated Hemoglobin 0303 health sciences Fructosylated hemoglobin Chromatography Dipeptide Chemistry Hydrophilic interaction chromatography FPOX assay 0104 chemical sciences HILIC-ESI-MS/MS Fructosamine Amine gas treating
Zdroj:	Analytical and Bioanalytical Chemistry
ISSN:	1618-2650 1618-2642
DOI:	10.1007/s00216-019-02186-2
Popis:	Naturally occurring fructosamines are of high clinical significance due to their potential use in diabetes mellitus monitoring (quantification of fructosylated hemoglobin, HbA1c) or for the investigation of their reactivity in consecutive reactions and harmfulness towards the organism. Here we report the specific synthesis of the fructosylated dipeptide l-valyl-l-histidine (Fru-Val-His) and fructosylated l-valine (Fru-Val). Both are basic tools for the development and validation of enzymatic HbA1c assays. The two fructosamine derivatives were synthesized via a protected glucosone intermediate which was coupled to the primary amine of Val or Val-His, performing a reductive amination reaction. Overall yields starting from fructose were 36% and 34% for Fru-Val and Fru-Val-His, respectively. Both compounds were achieved in purities > 90%. A HILIC-ESI-MS/MS method was developed for routine analysis of the synthesized fructosamines, including starting materials and intermediates. The presented method provides a well-defined and efficient synthesis protocol with purification steps and characterization of the desired products. The functionality of the fructosylated dipeptide has been thoroughly tested in an enzymatic HbA1c assay, showing its concentration-dependent oxidative degradation by fructosyl-peptide oxidases (FPOX).
Databáze:	OpenAIRE
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