Journal
MASS SPECTROMETRY REVIEWS
Volume 36, Issue 6, Pages 677-692Publisher
WILEY
DOI: 10.1002/mas.21491
Keywords
deamidation; PIMT; isoAsp; mass spectrometry; ERLIC; ECD
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Funding
- Singapore Ministry of Education [Tier 2: ARC9/15, Tier 1: RGT15/13]
- NTU-NHG [ARG/14017]
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Protein deamidation has been proposed to represent a molecular clock that progressively disrupts protein structure and function in human degenerative diseases and natural aging. Importantly, this spontaneous process can also modify therapeutic proteins by altering their purity, stability, bioactivity, and antigenicity during drug synthesis and storage. Deamidation occurs non-enzymatically in vivo, but can also take place spontaneously in vitro, hence artificial deamidation during proteomic sample preparation can hamper efforts to identify and quantify endogenous deamidation of complex proteomes. To overcome this, mass spectrometry (MS) can be used to conduct rigorous site-specific characterization of protein deamidation due to the high sensitivity, speed, and specificity offered by this technique. This article reviews recent progress in MS analysis of protein deamidation and discusses the strengths and limitations of common top-down and bottom-up approaches. Recent advances in sample preparation methods, chromatographic separation, MS technology, and data processing have for the first time enabled the accurate and reliable characterization of protein modifications in complex biological samples, yielding important new data on how deamidation occurs across the entire proteome of human cells and tissues. These technological advances will lead to a better understanding of how deamidation contributes to the pathology of biological aging and major degenerative diseases. (C) 2016 Wiley Periodicals, Inc.
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