Abstract It is demonstrated that HIV-1 protease is essential for the assembly and infectivity of the acquired immunodeficiency syndrome (AIDS) virus. This protease is an aspartyl protease with a 2-fold symmetry axis. Potential inhibitors were synthesized and consisted of a spacer linking 2 peptidic chains. They had to satisfy the following constraints: a C 2 symmetry axis, a backbone similar to the peptidic substrates, and side-chains filling the ...