Synthesis of peptide analogues containing phosphonamidate methyl ester functionality: HIV-1 proteinase inhibitors possessing unique cell uptake properties

Stereochemically defined and epimeric phosphonamidate methyl ester-containing peptide analogues were synthesised and were found to be moderate inhibitors of the HIV-1 proteinase. All of the analogues containing the phosphonamidate ester grouping showed a marked ability to enter cells, as highlighted by the approximate equivalence of the IC 50 values for enzyme inhibition in solution and inhibition of HIV-1 replication in virus infected cells. Phosphonamidate methyl ester containing peptide analogues [ eg. ( 6)] are moderate inhibitors of the HIV-1 proteinase but show a marked ability to enter virus infected cells.