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  • Title: Identification of hemoglobin variants by top-down mass spectrometry using selected diagnostic product ions.
    Author: Coelho Graça D, Hartmer R, Jabs W, Beris P, Clerici L, Stoermer C, Samii K, Hochstrasser D, Tsybin YO, Scherl A, Lescuyer P.
    Journal: Anal Bioanal Chem; 2015 Apr; 407(10):2837-45. PubMed ID: 25753013.
    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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