The potential of fractional diagonal chromatography strategies for the enrichment of post-translational modifications

• Only few of the >450 known PTMs can be enriched from complex samples.
• Comprehensive PTM analysis requires the development of novel methods.
• Fractional diagonal chromatography shows a strong potential for PTM enrichment.
• Alliance with affinity-based methods opens new avenues for studying PTM X-talk.

More than 450 post-translational modifications (PTMs) are known, however, currently only some of those can be enriched and analyzed from complex samples such as cell lysates. Therefore, we need additional methods and concepts to improve our understanding about the dynamic crosstalk of PTMs and the highly context-dependent regulation of protein function by so-called ‘PTM codes’. The mere focus on affinity-based enrichment techniques may not be sufficient to achieve this ambitious goal. However, the complementary use of two-dimensional chromatography-based strategies such as COFRADIC and ChaFRADIC might open new avenues for enriching a variety of so far inaccessible PTMs for large-scale proteome studies.

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