PYRROLINONE-BASED HIV PROTEASE INHIBITORS - DESIGN, SYNTHESIS, AND ANTIVIRAL ACTIVITY - EVIDENCE FOR IMPROVED TRANSPORT

Pyrrolinone-based peptidomimetics, the first mimics of beta-strands, a re potent inhibitors of HIV-1 protease. Importantly, the bis(pyrrolino nes) described herein proved to be more active in cellular antiviral a ssays compared with an analogous peptide-derived inhibitor even though they are less effective in inhibiting the isolated protease. These re sults suggest that pyrrolinone inhibitors offer better transport prope rties than the corresponding peptide-based peptidomimetics; we attribu te this effect to decreased solvation of the mimetics. Structure-activ ity relationships for the pyrrolinones correlate well with those repor ted for related peptides, consistent with similar modes of binding.