Probing lysine mono-methylation in histone H3 tail peptides with an abiotic receptor coupled to a non-plasmonic resonator

Binder and effector molecules that allow studying and manipulating epigenetic processes are of biological relevance and pose severe technical challenges. We report the first example of a synthetic receptor able to recognize mono-methylated lysines in a histone H3 tail peptide, which has relevant functions in epigenetic regulation. Recognition is robust and specific regardless of the position and the number of monomethylated lysines along the polypeptide chain. The peptide is first captured in solution by a tetraphosphonate cavitand (Tiiii) that selectively binds its Lys-NMe+ moieties. Separation from solution and detection of the peptide-Tiiii complexes is then enabled in one single step by an all dielectric SiO2–TiO2 core–shell resonator (T-rex), which captures the complex and operates fully reproducible signal transduction by non-plasmonic surface enhanced Raman scattering (SERS) without degrading the complex. The realized abiotic probe is able to distinguish multiple mono-methylated peptides from the single mono-methylated ones.