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A single protein to multiple peptides: Investigation of protein-peptide correlations using targeted alpha-2-macroglobulin analysis
Date
2023-08-01
Author
Yildiz, Pelin
Özcan Kabasakal, Süreyya
Metadata
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Recent advances in proteomics technologies have enabled the analysis of thousands of proteins in a high-throughput manner. Mass spectrometry (MS) based proteomics uses a peptide-centric approach where biological samples undergo specific proteolytic digestion and then only unique peptides are used for protein identification and quantification. Considering the fact that a single protein may have multiple unique peptides and a number of different forms, it becomes essential to understand dynamic protein-peptide relationships to ensure robust and reliable peptide-centric protein analysis. In this study, we investigated the correlation between protein concentration and corresponding unique peptide responses under a conventional proteolytic digestion condition. Protein-peptide correlation, digestion efficiency, matrix-effect, and concentration-effect were evaluated. Twelve unique peptides of alpha-2-macroglobulin (A2MG) were monitored using a targeted MS approach to acquire insights into protein-peptide dynamics. Although the peptide responses were reproducible between replicates, protein-peptide correlation was moderate in protein standards and low in complex matrices. The results suggest that reproducible peptide signal could be misleading in clinical studies and a peptide selection could dramatically change the outcome at protein level. This is the first study investigating quantitative protein-peptide correlations in biological samples using all unique peptides representing the same protein and opens a discussion on peptide-based proteomics.
Subject Keywords
Targeted proteomics
,
Mass spectrometry
,
Quantitative proteomics
,
Alpha-2-macroglobulin
,
Unique peptide
,
Serum
URI
https://hdl.handle.net/11511/104667
Journal
TALANTA
DOI
https://doi.org/10.1016/j.talanta.2023.124878
Collections
Department of Chemistry, Article
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IEEE
ACM
APA
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MLA
BibTeX
P. Yildiz and S. Özcan Kabasakal, “A single protein to multiple peptides: Investigation of protein-peptide correlations using targeted alpha-2-macroglobulin analysis,”
TALANTA
, no. 124878, pp. 1–13, 2023, Accessed: 00, 2023. [Online]. Available: https://hdl.handle.net/11511/104667.