Pyrrolinone-Based HIV Protease Inhibitors. Design, Synthesis, and Antiviral Activity: Evidence for Improved Transport

Pyrrolinone-based peptidomimetics, the first mimics of beta -strands, are potent inhibitors of HIV-1 protease. Importantly, the bis(pyrrolinones) described herein proved to be more active in cellular antiviral assays compared with an analogous peptide-derived inhibitor even though they are less effe...

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Bibliographic Details
Published in:Journal of the American Chemical Society 1995-11, Vol.117 (45), p.11113-11123
Main Authors: Smith, Amos B, Hirschmann, Ralph, Pasternak, Alexander, Guzman, Mark C, Yokoyama, Akihisa, Sprengeler, Paul A, Darke, Paul L, Emini, Emilio A, Schleif, William A
Format: Article
Language:English
Subjects:
human immunodeficiency virus 1
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Summary:Pyrrolinone-based peptidomimetics, the first mimics of beta -strands, are potent inhibitors of HIV-1 protease. Importantly, the bis(pyrrolinones) described herein proved to be more active in cellular antiviral assays compared with an analogous peptide-derived inhibitor even though they are less effective in inhibiting the isolated protease. These results suggest that pyrrolinone inhibitors offer better transport properties than the corresponding peptide-based peptidomimetics; we attribute this effect to decreased solvation of the mimetics. Structure-activity relationships for the pyrrolinones correlate well with those reported for related peptides, consistent with similar modes of binding.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja00150a011