New technique cracks cancer cell signaling by pinpointing exact protein modifications
Researchers have developed synthetic molecular filters that can detect where proteins are chemically modified inside cancer cells—solving a decades-old problem in cell biology. The breakthrough could accelerate drug discovery by revealing precisely how tumor cells communicate and respond to treatments.
Originaltitel: Proteoform-specific enrichment of phosphopeptide isomers by polymer-based synthetic receptors.
Malmö universitet presenterar en molekylär imprinting-teknik som löser ett långvarigt problem inom cancerforskningen: att särskilja närliggande fosforyleringssajter på proteiner. Konventionell fosfoproteomik missar låga concentrationer av peptider och kan inte skilja mellan isomerer — en kritisk begränsning när man kartlägger cellulär signalering. Forskarna utvecklade syntetiska receptorer baserade på imprinted polymerer för att selektivt fånga definierade fosfopeptidmotiv från cancercellproteom. Med ZAP70-kinase som modell kunde de lösa fosforylering vid två närliggande tyrosinresiduerna (pY492 och pY493) i ett regulatoriskt motiv — en genombrytning för sajt-upplösning. Integrerat med vätskekromatografi-masspektrometri möjliggör metoden känslig detektion av låg-abundanta, isomeriska peptider som traditionell berikelse missar. För leverantörer av analysservices och diagnostik öppnar denna plattform vägar att sälja högupplösta signalerings-karteringar för precision-onkologi redan inom 3–5 år.
Site-level resolution of protein phosphorylation remains a central challenge in decoding cellular signaling and conventional global phosphoproteomics is limited in its ability to detect low-abundance peptides and resolve positional isomers. Here we introduce sequence-selective synthetic receptors based on imprinted polymers for targeted enrichment of defined phosphopeptide motifs from complex cancer cell proteomes. By encoding local sequence context into the binding interface, these receptors enable selective capture of closely related phosphorylation sites with high specificity. Using the T cell kinase ZAP70 as a model, we resolve phosphorylation at adjacent tyrosine residues (pY492 and pY493) within a regulatory motif, overcoming a long-standing limitation in site discrimination. Integrated with liquid chromatography-mass spectrometry workflows, this enables sensitive detection of low-abundance and isomeric phosphopeptides that evade conventional enrichment strategies. More broadly, our findings establish molecular imprinting as a programmable chemical platform for site-resolved phosphoproteomics, opening new avenues to interrogate signaling networks with molecular precision.