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Protease inhibitors - Design
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Protease inhibitors - Design
Protease inhibitors were designed to mimic the transition state of the protease's actual substrates. A peptide linkage consisting of –NH-CO- is replaced by an hydroxyethylen group (-CH2-CH(OH)-) which the protease is unable to cleave. HIV protease inhibitors fit the active site of the HIV aspartic protease and were rationally designed utilizing knowledge of the aspartyl protease's mode of action. The most promising transition state mimic was hydroxyethylamine which led to the discovery of the first protease inhibitor, saquinavir.
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