Carboxypeptidases

Carboxypeptidase inhibitors target exopeptidases that trim the C-terminal residue from peptides and proteins. Most compounds here target glutamate carboxypeptidase II (GCPII), also called N-acetylated alpha-linked acidic dipeptidase (NAALADase). The enzyme cleaves the neuropeptide N-acetylaspartylglutamate (NAAG) into N-acetylaspartate and glutamate. A 1999 study reported that selective NAALADase inhibition with PMPA reduced ischemic brain injury in an animal model. The thiol-based inhibitor 2-MPPA was described in 2003 as an orally active GCPII inhibitor. ZJ 43 is a urea-based compound that inhibits both GCPII and the related glutamate carboxypeptidase III (GCPIII). The set also holds Histargin, a carboxypeptidase B inhibitor, and a carboxypeptidase G2 (CPG2) inhibitor for the bacterial folate-cleaving enzyme.