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Direct glucosone-based synthesis and HILIC-ESI-MS/MS characterization of N-terminal fructosylated valine and valylhistidine for validation of enzymatic HbA(1c) assays in the diagnosis of diabetes mellitus

Naturally occurring fructosamines are of high clinical significance due to their potential use in diabetes mellitus monitoring (quantification of fructosylated hemoglobin, HbA(1c)) or for the investigation of their reactivity in consecutive reactions and harmfulness towards the organism. Here we rep...

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Autores principales: Gerke, Christoph, Buchholz, Monika, Müller, Holger, Meusinger, Reinhard, Grimmler, Matthias, Metzmann, Erwin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920237/
https://www.ncbi.nlm.nih.gov/pubmed/31754770
http://dx.doi.org/10.1007/s00216-019-02186-2
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author Gerke, Christoph
Buchholz, Monika
Müller, Holger
Meusinger, Reinhard
Grimmler, Matthias
Metzmann, Erwin
author_facet Gerke, Christoph
Buchholz, Monika
Müller, Holger
Meusinger, Reinhard
Grimmler, Matthias
Metzmann, Erwin
author_sort Gerke, Christoph
collection PubMed
description Naturally occurring fructosamines are of high clinical significance due to their potential use in diabetes mellitus monitoring (quantification of fructosylated hemoglobin, HbA(1c)) 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 HbA(1c) 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 HbA(1c) assay, showing its concentration-dependent oxidative degradation by fructosyl-peptide oxidases (FPOX). [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00216-019-02186-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-69202372019-12-30 Direct glucosone-based synthesis and HILIC-ESI-MS/MS characterization of N-terminal fructosylated valine and valylhistidine for validation of enzymatic HbA(1c) assays in the diagnosis of diabetes mellitus Gerke, Christoph Buchholz, Monika Müller, Holger Meusinger, Reinhard Grimmler, Matthias Metzmann, Erwin Anal Bioanal Chem Paper in Forefront Naturally occurring fructosamines are of high clinical significance due to their potential use in diabetes mellitus monitoring (quantification of fructosylated hemoglobin, HbA(1c)) 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 HbA(1c) 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 HbA(1c) assay, showing its concentration-dependent oxidative degradation by fructosyl-peptide oxidases (FPOX). [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00216-019-02186-2) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2019-11-22 2019 /pmc/articles/PMC6920237/ /pubmed/31754770 http://dx.doi.org/10.1007/s00216-019-02186-2 Text en © The Author(s) 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Paper in Forefront
Gerke, Christoph
Buchholz, Monika
Müller, Holger
Meusinger, Reinhard
Grimmler, Matthias
Metzmann, Erwin
Direct glucosone-based synthesis and HILIC-ESI-MS/MS characterization of N-terminal fructosylated valine and valylhistidine for validation of enzymatic HbA(1c) assays in the diagnosis of diabetes mellitus
title Direct glucosone-based synthesis and HILIC-ESI-MS/MS characterization of N-terminal fructosylated valine and valylhistidine for validation of enzymatic HbA(1c) assays in the diagnosis of diabetes mellitus
title_full Direct glucosone-based synthesis and HILIC-ESI-MS/MS characterization of N-terminal fructosylated valine and valylhistidine for validation of enzymatic HbA(1c) assays in the diagnosis of diabetes mellitus
title_fullStr Direct glucosone-based synthesis and HILIC-ESI-MS/MS characterization of N-terminal fructosylated valine and valylhistidine for validation of enzymatic HbA(1c) assays in the diagnosis of diabetes mellitus
title_full_unstemmed Direct glucosone-based synthesis and HILIC-ESI-MS/MS characterization of N-terminal fructosylated valine and valylhistidine for validation of enzymatic HbA(1c) assays in the diagnosis of diabetes mellitus
title_short Direct glucosone-based synthesis and HILIC-ESI-MS/MS characterization of N-terminal fructosylated valine and valylhistidine for validation of enzymatic HbA(1c) assays in the diagnosis of diabetes mellitus
title_sort direct glucosone-based synthesis and hilic-esi-ms/ms characterization of n-terminal fructosylated valine and valylhistidine for validation of enzymatic hba(1c) assays in the diagnosis of diabetes mellitus
topic Paper in Forefront
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920237/
https://www.ncbi.nlm.nih.gov/pubmed/31754770
http://dx.doi.org/10.1007/s00216-019-02186-2
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