Proteoform-specific enrichment of phosphopeptide isomers by polymer-based synthetic receptors.

Polymer-based synthetic receptors achieve site-specific enrichment of phosphopeptide isomers, resolving adjacent phosphorylation sites with high precision in complex proteomes.

• Why it matters: Deciphering cellular signaling requires accurate identification of phosphorylation sites, but current methods struggle to detect low-abundance peptides and distinguish positional isomers, limiting understanding of signaling dynamics.
• What they did: The study developed sequence-selective imprinted polymers that target specific phosphopeptide motifs, enabling the selective capture of closely related phosphorylation sites, exemplified by resolving pY492 and pY493 in ZAP70.
• The result: This approach enhances detection sensitivity for low-abundance and isomeric phosphopeptides, providing a programmable platform for site-resolved phosphoproteomics and advancing the analysis of cellular signaling networks.