Abstract 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-1H- 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 ...