The mammalian proprotein convertase furin has been found to play an important role in diverse physiological and patho-logical events, such as the activation of viral glycoproteins and bacterial exotoxins. Small, non-toxic and highly active,furin inhibitors are considered to be attractive drug candi-dates for diseases caused by virus and bacteria. In this study,aseries of peptide inhibitors were designed and synthesized based on the C-terminal fragment of histone H1.2, which has an inhibitory effect on furin. Replacing the reactive site of inhibitors with the consensus substrate recognition sequence of furin has been found to increase inhibitory activity greatly.The most potent inhibitor, I4, with 14 amino acid residues has a Ki value of 17 nM for furin. Although most of the synthesized peptides were temporary inhibitors, the inhibitor Is, with nine amino adds, retained its full potency, even after a 3 h incubation period with furin at 37 ℃. These inhibitors may potentially lead to the development of anti-viral and anti-bacterial drug compounds.