Alpha-ketoamide Phe-Pro isostere as a new core structure for the inhibition of HIV protease
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Updated: Jan 30, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
1Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
Abstract:
Studies on the inhibition of HIV-1 protease utilizing a core isostere with replacement of the scissle bond for an alpha-amino-ketone have resulted in the development of an alpha-keto-amide isosteric replacement of the Phe-Pro scissle amide bond. The simple dipeptide isostere was shown to be a promising new core structure for the development of the enzyme inhibitors. The Ki of this core structure was determined to be 6 microM, compared to 230 microM and > 50 microM for the corresponding phosphinic acid and hydroxyethylamine isosteres.
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