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

Synthetic polymer-based receptors enable site-specific enrichment of phosphopeptide isomers, resolving adjacent phosphorylation sites in complex proteomes with high specificity.

• Why it matters: Deciphering cellular signaling requires precise identification of phosphorylation sites, but conventional methods struggle to detect low-abundance peptides and distinguish positional isomers, limiting understanding of signaling dynamics.
• What they did: Researchers developed sequence-selective synthetic receptors based on imprinted polymers that target phosphopeptide motifs, and applied them to complex cancer cell proteomes, focusing on the ZAP70 kinase model.
• The result: This approach allows sensitive detection of low-abundance and isomeric phosphopeptides, including adjacent tyrosine phosphorylation sites, advancing site-resolved phosphoproteomics and molecular-level signaling analysis.