Pseudopeptides with a centrally positioned alkene-based disulphide bridge mimetic stimulate kallikrein-related peptidase 3 activityElectronic supplementary information (ESI) available. See DOI: 10.1039/c3md20292e

Pseudopeptides based on the kallikrein-related peptidase 3 (KLK3) activating bicyclic peptide "C-4" comprising hydrocarbon-based disulphide bridge mimetics have been synthesized. After investigating different synthetic approaches, the pseudopeptides were successfully cyclized from two l -allylglycine side chains via an alkene ring-closing metathesis reaction during the peptide synthesis. The alkene-linker was formed in a 1 : 1 E / Z isomer ratio. The resulting pseudopeptides were almost as potent as the parent peptide, increasing the activity of KLK3 over four-fold at 200 μg ml −1 (130-140 μM) concentrations. First successful pseudopeptides of the KLK3-activating bicyclic peptide "C-4" are reported.