Glutamine-derived aldehydes for the inhibition of human rhinovirus 3C protease

Peptide aldehydes have been synthesized and evaluated as inhibitors of human rhinovirus 3C protease. Those inhibitors containing a C-terminal glutamine aldehyde were prepared using newly developed methodology involving reduction of the corresponding glutarimide, which can be easily prepared from N-protected glutamine. Low molecular weight (<500) compounds with low to submicromolar inhibitory activity in both isolated enzyme and in vitro translation assays have been identified.