Identification of hemoglobin variants by top-down mass spectrometry using selected diagnostic product ions

Analytical and Bioanalytical Chemistry
Didia Coelho GraçaPierre Lescuyer

Abstract

Hemoglobin disorder diagnosis is a complex procedure combining several analytical steps. Due to the lack of specificity of the currently used protein analysis methods, the identification of uncommon hemoglobin variants (proteoforms) can become a hard task to accomplish. The aim of this work was to develop a mass spectrometry-based approach to quickly identify mutated protein sequences within globin chain variants. To reach this goal, a top-down electron transfer dissociation mass spectrometry method was developed for hemoglobin β chain analysis. A diagnostic product ion list was established with a color code strategy allowing to quickly and specifically localize a mutation in the hemoglobin β chain sequence. The method was applied to the analysis of rare hemoglobin β chain variants and an (A)γ-β fusion protein. The results showed that the developed data analysis process allows fast and reliable interpretation of top-down electron transfer dissociation mass spectra by nonexpert users in the clinical area.

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Citations

Jun 17, 2016·Annual Review of Analytical Chemistry·Timothy K TobyNeil L Kelleher
Nov 16, 2019·Proteomics·Constance A SobseyChristoph H Borchers
Jul 26, 2021·Analytical Biochemistry·Pushpanjali DasauniSuman Kundu
Feb 6, 2017·Journal of Proteome Research·Luca FornelliNeil L Kelleher
Dec 28, 2021·Journal of the American Society for Mass Spectrometry·Yuan LinLissa C Anderson

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