Small peptidic aldehyde inhibitors of human rhinovirus 3C protease

Small peptide aldehydes were designed to mimic the preferred substrate requirements for the human rhinovirus 3C protease. Di- and tripeptide aldehydes containing a methionine sulfone as a P1 surrogate for glutamine show low micromolar enzyme inhibitory and antiviral tissue culture activity. LY338387, obtained in a short and efficient synthesis, appears to validate the protease as a therapeutic target.