Polyozellin, a New Inhibitor of Prolyl Endopeptidase from Polyozellus multiplex.

Prolyl endopeptidase (PEP, EC 3.4.21.26) is a serine protease which is knownto cleave a peptide substrate in the C-terminal side of a proline residue1'2).In the central nervous system, PEP degrades proline-containing neuropeptides such as vasopressin, substance P, and thyrotropin-releasing hormone (TRH) which has been suggested to play an important role in learning and memory3 ~5).In addition, recent studies suggest that PEP could be implicated in the processing the C-terminal portion of the amyloid precursor protein in Alzheimer's disease6).It is also reported that cognitive deficits in