Determination of free desmosine and isodesmosine as urinary biomarkers of lung disorder using ultra performance liquid chromatography–ion mobility-mass spectrometry

Devenport, Neil A.; Reynolds, James C.; Parkash, Ved; Cook, Jason R.; Weston, Daniel J.; Creaser, Colin S.

doi:10.1016/j.jchromb.2011.10.016

Cited by 16 publications

(11 citation statements)

References 31 publications

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“…Each of these dilutions was analyzed in quadruplicate. Moreover, because in vivo, Des and Isodes occur in equimolar amounts [38], we mimicked this condition by investigating equimolar concentration ratios of Des and Isodes. These were studied over a concentration range of 125 ng/μL to 3.125 ng/μL mixed with 25 ng/μL of Labeled-Des.…”

Section: Resultsmentioning

confidence: 99%

Quantification of desmosine and isodesmosine using MALDI-ion trap tandem mass spectrometry

Rathod

Kaur

et al. 2018

Anal Bioanal Chem

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Desmosine (Des) and isodesmosine (Isodes), cross-linking amino acids in the biomolecule elastin, may be used as biomarkers for various pathological conditions associated with elastin degradation. The current study presents a novel approach to quantify Des and Isodes using matrix-assisted laser desorption ionization (MALDI)-tandem mass spectrometry (MS) in a linear ion trap coupled to a vacuum MALDI source. MALDI-MS analyses of Des and Isodes are performed using stable-isotope-labeled desmosine d (labeled-Des) as an internal standard in different biological fluids, such as urine and serum. The method demonstrated linearity over two orders of magnitude with a detection limit of 0.02 ng/μL in both urine and serum without enrichment prior to mass spectrometry, and relative standard deviation of < 5%. The method is used to evaluate the time-dependent degradation of Des upon UV irradiation (254 nm) and found to be consistent with quantification by H NMR. This is the first characterized MALDI-MS method for quantification of Des and Isodes and illustrates the potential of MALDI-ion trap MS for effective quantification of biomolecules. The reported method represents improvement over current liquid chromatography-based methods with respect to analysis time and solvent consumption, while maintaining similar analytical characteristics. Graphical abstract ᅟ.

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Section: Resultsmentioning

confidence: 99%

Quantification of desmosine and isodesmosine using MALDI-ion trap tandem mass spectrometry

Rathod

Kaur

et al. 2018

Anal Bioanal Chem

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“…Desmosine is a rare amino acid produced by elastin breakdown. The release of desmosine is accelerated in patients with inflammatory conditions such as chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB) [24–29]. SolanesylPP is predicted to be the strongest binder among the ligands selected.…”

Section: Resultsmentioning

confidence: 99%

Systematic discovery of molecular probes targeting multiple non-orthosteric and spatially distinct sites in the botulinum neurotoxin subtype A (BoNT/A)

Dadgar

Floriano

2015

Molecular and Cellular Probes

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The development of molecular probes targeting proteins has traditionally relied on labeling compounds already known to bind to the protein of interest. These known ligands bind to orthosteric or allosteric sites in their target protein as a way to control their activity. Binding pockets other than known orthosteric or allosteric sites may exist that are large enough to accommodate a ligand without significantly disrupting protein activity. Such sites may provide opportunities to discriminate between subtypes or other closely related proteins, since they are under less evolutionary pressure to be conserved. The Protein Scanning with Virtual Ligand Screening (PSVLS) approach was previously used to identify a novel inhibitor and a fluorescent probe against the catalytic site of the botulinum neurotoxin subtype A (BoNT/A). PSVLS screens compound databases against multiple sites within a target protein, and the results for all the sites probed against BoNT/A, not only the catalytic site, are available online. Here, we analyze the PSVLS data for multiple sites in order to identify molecular probes with affinity for binding pockets other than the catalytic site of BoNT/A. BoNT/A is a large protein with a light (LC) and a heavy (HC) chain that can be assayed separately. We used scintillation proximity assay (SPA) to test experimentally 5 probe candidates predicted computationally to have affinity for different non-orthosteric binding regions within the HC and LC, and one compound predicted not to have affinity for either domain. The binding profiles obtained experimentally confirmed the targeting of multiple and spatially distinct pockets within BoNT/A. Moreover, inhibition assay results indicate that some of these probes do not significantly interfere with the catalytic activity of BoNT/A.

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“…These factors making them potentially good biomarkers are assessed using Ultra Performance Liquid Chromatography-Ion MobilityMass Spectrometry (UPLC-IM-MS). Results have shown a higher concentration in COPD affected individuals when compared to healthy ones 36 . One study suggest that impulse oscillometry can assess the within breath behaviour of the oscillatory mechanics with high temporal resolution, which may be helpful for evaluating the severity of COPD (ref.…”

Section: Biomarkersmentioning

confidence: 90%

Respiratory muscle assessment in acute exacerbation of chronic obstructive pulmonary disease and its role as a potential biomarker

Vimal¹,

Kolek²,

Jaskova³

2012

BIOMED PAP

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Background. AECOPD is a life threatening condition for patients with chronic obstructive pulmonary disease (COPD) and lack of specific biomarker hinders effective management. Sputum, blood, breath and urinary biomarkers have all been investigated. We measured maximum respiratory pressure post exacerbation once the patient was compliant with the test and after 6 weeks, to assess any correlations. Methods and Results. The maximum pressures were measured using a closed circuit spirometer with a clean rubber mouthpiece properly placed with the patients lips sealed around it. Patients were properly instructed to exhale slowly and completely, then inspire with maximum possible effort and advised to keep it for nearly 1.5 s for maximum inspiratory pressure (MIP). For maximum expiratory pressures (MEP) patients were instructed to inspire slowly and completely, then expire forcefully with maximum effort. With the recorded values TTI (time tension index) was calculated. This was repeated again after 6 weeks. Using Pearsons correlation coefficient we found that MIP had a negative correlation with TTI and a positive correlation with FEV1. FEV1 had a positive correlation with FVC. MEP showed no significant correlation with TTI, but a positive correlation with FEV1. Conclusion. Acute exacerbations of COPD has a profound effect on the respiratory musculature especially the expiratory muscles but the maximum pressures are not specific enough to be prognostic markers. It might be worthwhile studying transformations of the respiratory musculature at the molecular level. More studies must be conducted to find a specific marker to aid in the management of the condition.

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Determination of free desmosine and isodesmosine as urinary biomarkers of lung disorder using ultra performance liquid chromatography–ion mobility-mass spectrometry

Cited by 16 publications

References 31 publications

Quantification of desmosine and isodesmosine using MALDI-ion trap tandem mass spectrometry

Quantification of desmosine and isodesmosine using MALDI-ion trap tandem mass spectrometry

Systematic discovery of molecular probes targeting multiple non-orthosteric and spatially distinct sites in the botulinum neurotoxin subtype A (BoNT/A)

Respiratory muscle assessment in acute exacerbation of chronic obstructive pulmonary disease and its role as a potential biomarker

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