General solid-phase synthesis approach to prepare mechanism-based aspartyl protease inhibitor libraries: identification of potent cathepsin D inhibitors

A method for the solid-phase synthesis of aspartyl protease inhibitors that do not incorporate any amino acids is presented. Several potent small molecule inhibitors were identified when a library of 204 spatially separate prepared compounds were screened against cathepsin D. The solid-phase synthesis approach was found to be capable of rapidly identifying small molecule inhibitors to diverse aspartyl protease targets.