Automated parallel derivatization of metabolites with SWATH-MS data acquisition for qualitative and quantitative analysis

Girard, Maria Fernanda Cifuentes; Ruskic, David; Böhm, Günter; Picenoni, Renzo; Hopfgartner, Gérard

doi:10.1016/j.aca.2020.06.030

Cited by 16 publications

(8 citation statements)

References 20 publications

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“…Such acquisition methods referred to as data independent acquisition (DIA) including the SWATH (accounting for Sequential Window Acquisition of all Theoretical fragment-ion spectra) approach are being increasingly used in metabolomics by enabling simultaneous metabolite identification and quantification through the acquisition of MS/MS spectra for all analytes in a single run [131,132]. Although slightly less sensitive than traditional LC-HRMS or MRM approaches, recent publications highlighted the potential of SWATH approaches for unambiguous compound detection and accurate quantification in complex samples [133][134][135][136]. With constant instrumental improvements (e.g., data acquisition speed on Orbitrap mass analyzers, in collision e n e r g i e s m a n a g e m e n t , se n s i t i v i t y , MS 2 spectra deconvolution), one can imagine great potential of such approach for future biological metabolomics applications.…”

Section: Analytical Validation Of Biomarker Candidates Highlighted By Untargeted Metabolomics: the Need For Targeted Quantitative Metabolmentioning

confidence: 99%

Metabolomics for personalized medicine: the input of analytical chemistry from biomarker discovery to point-of-care tests

et al. 2021

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Metabolomics refers to the large-scale detection, quantification, and analysis of small molecules (metabolites) in biological media. Although metabolomics, alone or combined with other omics data, has already demonstrated its relevance for patient stratification in the frame of research projects and clinical studies, much remains to be done to move this approach to the clinical practice. This is especially true in the perspective of being applied to personalized/precision medicine, which aims at stratifying patients according to their risk of developing diseases, and tailoring medical treatments of patients according to individual characteristics in order to improve their efficacy and limit their toxicity. In this review article, we discuss the main challenges linked to analytical chemistry that need to be addressed to foster the implementation of metabolomics in the clinics and the use of the data produced by this approach in personalized medicine. First of all, there are already well-known issues related to untargeted metabolomics workflows at the levels of data production (lack of standardization), metabolite identification (small proportion of annotated features and identified metabolites), and data processing (from automatic detection of features to multi-omic data integration) that hamper the inter-operability and reusability of metabolomics data. Furthermore, the outputs of metabolomics workflows are complex molecular signatures of few tens of metabolites, often with small abundance variations, and obtained with expensive laboratory equipment. It is thus necessary to simplify these molecular signatures so that they can be produced and used in the field. This last point, which is still poorly addressed by the metabolomics community, may be crucial in a near future with the increased availability of molecular signatures of medical relevance and the increased societal demand for participatory medicine. Graphical abstract

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Section: Analytical Validation Of Biomarker Candidates Highlighted By Untargeted Metabolomics: the Need For Targeted Quantitative Metabolmentioning

confidence: 99%

Metabolomics for personalized medicine: the input of analytical chemistry from biomarker discovery to point-of-care tests

et al. 2021

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“…We performed proteolytic stability studies in human blood serum to investigate whether the introduction of urea bonds affected the half-lives of compounds from each of synthesized group of hybrids. Compounds 3, 6 and 7 were incubated with human serum at 37 • C. Samples were taken at different time intervals and analyzed using LC-SWATH-MS [88][89][90]. Identified cleavage sites were compared with the degradation of the parent peptide, which exhibited a half-life of 8 h. Hybrids 6 and 7 were stable toward enzymatic degradation, with 50% of each compound still being intact after 96 h (Figure 5).…”

Section: In Vitro Enzymatic Stabilitymentioning

confidence: 99%

Urea-Peptide Hybrids as VEGF-A165/NRP-1 Complex Inhibitors with Improved Receptor Affinity and Biological Properties

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Sosnowski

Hermine

et al. 2020

IJMS

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Neuropilin-1 (NRP-1), the major co-receptor of vascular endothelial growth factor receptor-2 (VEGFR-2), may also independently act with VEGF-A165 to stimulate tumour growth and metastasis. Therefore, there is great interest in compounds that can block VEGF-A165/NRP-1 interaction. Peptidomimetic type inhibitors represent a promising strategy in the treatment of NRP-1-related disorders. Here, we present the synthesis, affinity, enzymatic stability, molecular modeling and in vitro binding evaluation of the branched urea–peptide hybrids, based on our previously reported Lys(hArg)-Dab-Oic-Arg active sequence, where the Lys(hArg) branching has been modified by introducing urea units to replace the peptide bond at various positions. One of the resulting hybrids increased the affinity of the compound for NRP-1 more than 10-fold, while simultaneously improving resistance for proteolytic stability in serum. In addition, ligand binding to NRP-1 induced rapid protein stock exocytotic trafficking to the plasma membrane in breast cancer cells. Examined properties characterize this compound as a good candidate for further development of VEGF165/NRP-1 inhibitors.

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“…Various methods of solvent extractions or derivatizations were developed to handle a diverse set of metabolites of different polarities and chemical properties. [ 11–13 ] Mixtures of acetonitrile, methanol and water are often used for extraction of more polar metabolites. For instance, a mixture of 40:40:20 (v/v/v) acetonitrile:methanol:water with 0.1 m formic acid, followed by addition of bicarbonate was applied to harvest high‐energy compounds like NADPH and ATP.…”

Section: Introductionmentioning

confidence: 99%

“…[ 16,18 ] Derivatization methods were also extensively used to enhance the ionization efficiency of compounds of limiting endogenous abundance, high chemical instability, or low‐ionization efficiency. [ 11–13,19 ]…”

Section: Introductionmentioning

confidence: 99%

Precise Metabolomics Reveals a Diversity of Aging‐Associated Metabolic Features

et al. 2022

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Mass spectrometry‐based metabolomics has emerged as a powerful technique for biomedical research, although technical issues with its analytical precision and structural characterization remain. Herein, a robust non‐targeted strategy for accurate quantitation and precise profiling of metabolomes is developed and applied to investigate plasma metabolic features associated with human aging. A comprehensive set of isotope‐labeled standards (ISs) covering major metabolic pathways is incorporated to quantify polar metabolites. Matching rules to select ISs for calibration follow a primary criterion of minimal coefficients of variations (COVs). If minimal COVs between specific ISs for a particular metabolite fall within 5% window, a further selection of ISs is conducted based on structural similarities and proximity in retention time. The introduction and refined selection of appropriate ISs for quantitation reduces the COVs of 480 identified metabolites in quality control samples from 14.3% to 9.8% and facilitates identification of additional metabolite. Finally, the precise metabolomics approach reveals perturbations in a diverse array of metabolic pathways across aging that principally implicate steroid metabolism, amino acid metabolism, lipid metabolism, and purine metabolism, which allows the authors to draw correlates to the pathology of various age‐related diseases. These findings provide clues for the prevention and treatment of these age‐related diseases.

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Automated parallel derivatization of metabolites with SWATH-MS data acquisition for qualitative and quantitative analysis

Cited by 16 publications

References 20 publications

Metabolomics for personalized medicine: the input of analytical chemistry from biomarker discovery to point-of-care tests

Metabolomics for personalized medicine: the input of analytical chemistry from biomarker discovery to point-of-care tests

Urea-Peptide Hybrids as VEGF-A165/NRP-1 Complex Inhibitors with Improved Receptor Affinity and Biological Properties

Precise Metabolomics Reveals a Diversity of Aging‐Associated Metabolic Features

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