Targeting the dimerization interface for irreversible inhibition of HIV-1 protease

A novel strategy was used to irreversibly inhibit HIV-1 protease. The inhibitor was designed to form a disulfide bond with Cys95, present at the dimerization interface of HIV-1 protease. The inhibitor was shown to be active against HIV-1 protease with Kinact=3.7 μM and Vinact=0.012 min−1.