Recent advances in top-down proteome sample processing ahead of MS analysis.

Autor: Nickerson JL; Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, Canada., Baghalabadi V; Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, Canada., Rajendran SRCK; Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, Canada.; Verschuren Centre for Sustainability in Energy and the Environment, Sydney, Nova Scotia, Canada., Jakubec PJ; Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, Canada., Said H; Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, Canada., McMillen TS; Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, Canada., Dang Z; Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, Canada., Doucette AA; Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, Canada.
Jazyk: angličtina
Zdroj: Mass spectrometry reviews [Mass Spectrom Rev] 2023 Mar; Vol. 42 (2), pp. 457-495. Date of Electronic Publication: 2021 May 28.
DOI: 10.1002/mas.21706
Abstrakt: Top-down proteomics is emerging as a preferred approach to investigate biological systems, with objectives ranging from the detailed assessment of a single protein therapeutic, to the complete characterization of every possible protein including their modifications, which define the human proteoform. Given the controlling influence of protein modifications on their biological function, understanding how gene products manifest or respond to disease is most precisely achieved by characterization at the intact protein level. Top-down mass spectrometry (MS) analysis of proteins entails unique challenges associated with processing whole proteins while maintaining their integrity throughout the processes of extraction, enrichment, purification, and fractionation. Recent advances in each of these critical front-end preparation processes, including minimalistic workflows, have greatly expanded the capacity of MS for top-down proteome analysis. Acknowledging the many contributions in MS technology and sample processing, the present review aims to highlight the diverse strategies that have forged a pathway for top-down proteomics. We comprehensively discuss the evolution of front-end workflows that today facilitate optimal characterization of proteoform-driven biology, including a brief description of the clinical applications that have motivated these impactful contributions.
(© 2021 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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