Novel pseudosymmetric inhibitors of HIV-1 protease

Abstract Compounds containing the easily accessible Phe[CH(OH)CH 2 N(NH)Phe dipeptide isostere as a non-hydrolyzable replacement of the scissile amide bond in the natural substrate are potent inhibitors of HIV-1 protease. The expected symmetric binding pattern of the most potent inhibitor in this series (CGP 53280, IC 50 = 9 nM) is illustrated by the X-ray analysis performed with the corresponding enzyme-inhibitor complex.