New Opportunities and Challenges of Smart Polymers in Post‐Translational Modification Proteomics

Protein post‐translational modifications (PTMs), which denote covalent additions of various functional groups (e.g., phosphate, glycan, methyl, or ubiquitin) to proteins, significantly increase protein complexity and diversity. PTMs play crucial roles in the regulation of protein functions and numerous cellular processes. However, in a living organism, native PTM proteins are typically present at substoichiometric levels, considerably impeding mass‐spectrometry‐based analyses and identification. Over the past decade, the demand for in‐depth PTM proteomics studies has spawned a variety of selective affinity materials capable of capturing trace amounts of PTM peptides from highly complex biosamples. However, novel design ideas or strategies are urgently required for fulfilling the increasingly complex and accurate requirements of PTM proteomics analysis, which can hardly be met by using conventional enrichment materials. Considering two typical types of protein PTMs, phosphorylation and glycosylation, an overview of polymeric enrichment materials is provided here, with an emphasis on the superiority of smart‐polymer‐based materials that can function in intelligent modes. Moreover, some smart separation materials are introduced to demonstrate the enticing prospects and the challenges of smart polymers applied in PTM proteomics.