Aminopeptidase inhibitory properties and analgesic activity of (2S,3R)-3,7-diamino-2-hydroxy-heptanoic acid containing tripeptide analogues of the N-terminal tripeptide of probestin.

(2S,3R)-3,7-Diamino-2-hydroxy-heptanoyl-Leu-Pro-OH [(2S,3R)-DAHHA-Leu-Pro-OH, 4], analogue of the N-terminal tripeptide of probestin, has been synthesized, and tested as inhibitor of AP-B, Leu-AP, AP-M, and enkephalin-degrading APs, and as analgesic. In order to establish structure-activity relationships the dipeptide (2S,3R)-DAHHA-Pro-OH (5) and the tripeptide (2S,3R)-DAHHA-Ala-Pro-OH (6) were also prepared. Compounds 4 and 6 were potent and selective inhibitors of enkephalin-degrading APs and showed a prolonged antinociceptive effect.