Protein Oxidation in Some Age‐Related Diseases

doi:10.1002/9781118493038.ch4

Cited by 1 publication

(2 citation statements)

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“…We further established the applicability of the aforementioned methodology to study oxidized tryptophan-containing peptides as an example of the extensibility of rPTMDetermine. Oxidation is important in a range of pathological conditions, including neurodegenerative diseases . Confident identification of oxidized peptides remains challenging, however, because oxidation may also target other residues (commonly phenylalanine, tyrosine, proline, and methionine); , these residues were considered as possible alternative oxidation sites during localization and the site probability criterion, nonetheless representing significant localization in all permutations.…”

Section: Resultsmentioning

confidence: 99%

“…Oxidation is important in a range of pathological conditions, including neurodegenerative diseases. 34 Confident identification of oxidized peptides remains challenging, however, because oxidation may also target other residues (commonly phenylalanine, tyrosine, proline, and methionine); 16,35 these residues were considered as possible alternative oxidation sites during localization and the site probability criterion, nonetheless representing significant localization in all permutations. As an example, we explored this modification at tryptophan (Scheme S2) to demonstrate the extensibility of our approach.…”

Section: Analytical Chemistrymentioning

confidence: 99%

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rPTMDetermine: A Fully Automated Methodology for Endogenous Tyrosine Nitration Validation, Site-Localization, and Beyond

et al. 2020

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We present herein rPTMDetermine, an adaptive and fully automated methodology for validation of the identification of rarely occurring post-translational modifications (PTMs), using a semisupervised approach with a linear discriminant analysis (LDA) algorithm. With this strategy, verification is enhanced through similarity scoring of tandem mass spectrometry (MS/MS) comparisons between modified peptides and their unmodified analogues. We applied rPTMDetermine to (1) perform fully automated validation steps for modified peptides identified from an in silico database and (2) retrieve potential yet-to-be-identified modified peptides from raw data (that had been missed through conventional database searches). In part (1), 99 of 125 3-nitrotyrosyl-containing (nitrated) peptides obtained from a ProteinPilot search were validated and localized. Twenty nitrated peptides were falsely assigned because of incorrect monoisotopic peak assignments, leading to erroneous identification of deamidation and nitration. Five additional nitrated peptides were, however, validated after performing nonmonoisotopic peak correction. In part (2), an additional 236 unique nitrated peptides were retrieved and localized, containing 113 previously unreported nitration sites; 25 endogenous nitrated peptides with novel sites were selected and verified by comparison with synthetic analogues. In summary, we identified and confidently validated 296 unique nitrated peptidescollectively representing the largest number of endogenously identified 3-nitrotyrosyl-containing peptides from the cerebral cortex proteome of a Macaca fascicularis model of stroke. Furthermore, we harnessed the rPTMDetermine strategy to complement conventional database searching and enhance the confidence of assigning rarely occurring PTMs, while recovering many missed peptides. In a final demonstration, we successfully extended the application of rPTMDetermine to peptides featuring tryptophan oxidation.

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Section: Resultsmentioning

confidence: 99%

Section: Analytical Chemistrymentioning

confidence: 99%