Functional Dihydro‐1 H ‐Imidazole Derivatives for MALDI Signal Enhancement of a Lysine‐Specific Chemical Modification

The enhancement of signal sensitivity and quantification of low‐abundance proteins is of great importance in proteomic analysis. The preparation of 2‐methoxy‐4,5‐dihydro‐1 H ‐imidazole (MeO‐DHIM) derivatives was accomplished by one‐step synthesis of O ‐methyl‐isourea. The signal enhancement induced by these attached moieties increases in an order of compound 1 ≈ 4 < 2 < 5 ≈ 6 < 3 in MALDI mass spectrometry. Peptide‐compound 3 adduct was approximately 20 times signal enhancement of the unmodified peptide and of 9 times of the peptide‐compound 1 adduct. This result demonstrates that the rational designed organic molecules are capable of providing a sensitive tool in the detection of low‐abundance proteins in proteomics.