We have synthesized and evaluated a small set of dual action HIV-Protease inhibitors, consisting of a catalytic site reversible inhibitor conjugated with a dimerization peptidic inhibitor, linked via a suitable selective end-modified poly(ethylene glycol), in an effort to obtain a synergistic effect with improved biological behaviour and more powerful pharmacological features, such as water solubility and cell permeability. Low nanomolar activity and synergism were obtained by coupling a Phenylalanine – Proline pseudopeptide catalytic site inhibitor and the Val-Val-Phe tripeptide dimerization inhibitor.
