Identification and characterization of post-translational modifications: Clinical implications

Abstract

Post-translational modifications (PTMs) generate marginally modified isoforms of native peptides, proteins and lipoproteins thereby regulating protein functions, molecular interactions, and localization. With a key role in functional proteomics, post-translational modifications are recently also associated with the onsets and progressions of various diseases, such as cancer, cardiovascular, renal, and metabolic diseases. With the impact of post-translational modifications becoming increasingly clear, its reliable detection and quantification remain a major obstacle in the translation of these novel pathological markers into clinical diagnosis. While current antibody-based clinical diagnostics struggle to detect and quantify these marginal protein and lipoprotein alterations, state-of-the-art mass spectrometric, proteomic approaches provide the mass accuracy and resolving power necessary to isolate, identify and quantify novel and pathological post-translational modifications; however clinical translation of mass spectrometric applications are still facing major challenges. Here we review the status quo of the clinical translation of mass-spectrometric applications as novel diagnostic tools for the identification and quantification of post-translational modifications and focus on the emerging role of mass spectrometric methods in the clinical assessment of PTMs in disease states.