Prolyl peptidases: a serine protease subfamily with high potential for drug discovery

Curr Opin Chem Biol. 2003 Aug;7(4):496-504. doi: 10.1016/s1367-5931(03)00084-x.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Carboxypeptidases / metabolism
  • Diabetes Mellitus / drug therapy
  • Dipeptidases / antagonists & inhibitors
  • Dipeptidases / chemistry
  • Dipeptidases / metabolism*
  • Dipeptidyl Peptidase 4 / chemistry
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism
  • Drug Delivery Systems
  • Gelatinases*
  • Humans
  • Membrane Proteins / metabolism
  • Peptide Hormones / metabolism
  • Prolyl Oligopeptidases
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / therapeutic use
  • Substrate Specificity


  • Membrane Proteins
  • Peptide Hormones
  • Serine Proteinase Inhibitors
  • Carboxypeptidases
  • Dipeptidases
  • proline dipeptidase
  • DPP9 protein, human
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Dipeptidyl Peptidase 4
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • seprase, human
  • PREPL protein, human
  • Prolyl Oligopeptidases
  • Gelatinases