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Prolyl endopeptidase (PREP) inhibitors target a serine protease that cuts short peptides after proline. The cytosolic enzyme is also known in the literature as prolyl oligopeptidase (POP). A seven-bladed beta-propeller domain covers the catalytic site and admits only peptides of about 30 residues or fewer. Reported substrates include neuropeptides such as substance P, arginine vasopressin and thyrotropin-releasing hormone. PREP also binds alpha-synuclein, and KYP-2047 lowers alpha-synuclein aggregates in cell and mouse models of Parkinson's disease. Next to inhibitors such as KYP-2047, Y-29794 oxalate and SUAM 1221, the section lists the chromogenic p-nitroanilide (pNA) substrates Z-Gly-Pro-pNA and Suc-Ala-Pro-pNA for activity assays.
