title: Design and evaluation of inhibitors of enkephalin degrading enzymes.
abstract: The endogenous opioid peptides enkephalins are degraded in vitro by several metallopeptidases (aminopeptidases, enkephalinase, dipeptidylaminopeptidases). Selective and mixed inhibitors of these enzymes were obtained by a rational approach taking into account crystallographic data on Thermolysin, a bacterial enzyme, used as model of metallopeptidase active site. This strategy is supported by recent cloning of enkephalinase. As expected, a physiological analgesia is produced by administration of inhibitors, especially kelatorphan and analogues, demonstrating unambiguously the implication of enkephalinase and aminopeptidase M in enkephalin metabolism. The intensive studies on endogenous opioid system have shown that inhibitors of enkephalin metabolism represent very useful probes and promising new analgesics.
authors.affiliation: Département de Chimie Organique, U 266 INSERM, UA 498 CNRS, UER des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Fournie-Zaluski