title: Prolyl peptidases: a serine protease subfamily with high potential for drug discovery.
abstract: Much attention has recently been given to a class of proteases that cleave proteins and peptides after proline residues. This class includes dipeptidyl peptidase IV (DPP IV; also termed CD26), fibroblast activation protein alpha (FAP; seprase), DPP7 (DPP II; quiescent cell proline dipeptidase), DPP8, DPP9, and prolyl carboxypeptidase (PCP; angiotensinase C). More distant members include prolyl oligopeptidase (POP; post proline cleaving enzyme) and acylaminoacylpeptidase (AAP; acylpeptide hydrolase). The DPPs and related proteins contain both membrane-bound and soluble members and span a broad range of expression patterns, tissue distributions and compartmentalization. These proteins have important roles in regulation of signaling by peptide hormones, and are emerging targets for diabetes, oncology and other indications.
authors.affiliation: ActivX Biosciences, Inc., 11025 North Torrey Pines Rd, La Jolla, CA 92037, USA. jonr@activx.xom
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Rosenblum
authors.forename: John W
authors.initials: JW
authors.lastname: Kozarich
mesh_terms: D000818:Animals; D002268:Carboxypeptidases / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy; D004150:Dipeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000378:metabolism; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism; D016503:Drug Delivery Systems; D010450:Endopeptidases; D018093:Gelatinases; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D036361:Peptide Hormones / Q000378:metabolism; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D013379:Substrate Specificity; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D002268:Carboxypeptidases; D004150:Dipeptidases; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D036361:Peptide Hormones; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors; D000099167:Fibroblast Activation Protein Alpha; C022449:proline dipeptidase; C471241:DPP9 protein, human; C478147:seprase, human; C000705287:PREPL protein, human