Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

The Prolyl-Aminodipeptidases and their Inhibitors as Therapeutic Targets for Fibrogenic Disorders

Author(s): Lucienne Juillerat-Jeanneret and Sandrine Gerber-Lemaire

Volume 9, Issue 2, 2009

Page: [215 - 226] Pages: 12

DOI: 10.2174/138955709787316100

Price: $65

Abstract

Many biologically active peptides are protected from general proteolytic degradation by evolutionary conserved prolines (Pro), due to conformational constraints imposed by the Pro residue. Thus the biological importance of prolyl-specific peptidases points to a high potential for drug discovery for this family of enzymes. Panels of inhibitors have been synthesized and their effects, determined in biological models, suggest the inhibition of families of enzymes with similar activities. Prolyl-specific aminodipeptidases include dipeptidyl-aminodipeptidase IV (DPP IV)/CD26, DPP8, DPP9 and fibroblast activation protease-α (FAP-α)/seprase, able to release X-Pro dipeptides from the N-terminus of peptides. DPP IV inhibitors are in clinical use for type 2 diabetes. In this review, the expression and the potential functions of prolyl-aminodipeptidases are reviewed in diseases, and the inhibitors developed for these enzymes are discussed, with a specific focus on inhibitors able to discriminate between DPP IV and fibroblast activation protease-α (FAPα)/seprase as potential leads for the treatment of fibrogenic diseases.

Keywords: Diabetes, dipeptidyl-aminodipeptidase IV, fibroblast activation protease-α, fibrogenic disorders, specific inhibition


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy