title: 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.
abstract: (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.
authors.affiliation: Instituto de Química Médica, C.S.I.C., Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Herranz
authors.forename: S
authors.initials: S
authors.lastname: Vinuesa
authors.forename: C
authors.initials: C
authors.lastname: Pérez
authors.forename: M T
authors.initials: MT
authors.lastname: García-López
authors.forename: M L
authors.initials: ML
authors.lastname: De Ceballos
authors.forename: F M
authors.initials: FM
authors.lastname: Murillo
authors.forename: J
authors.initials: J
authors.lastname: del Río
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D006538:Heptanoic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D006538:Heptanoic Acids; D009842:Oligopeptides; C063432:probestin; C077161:3,7-diamino-2-hydroxyheptanoyl-leucyl-proline; C077162:3,7-diamino-2-hydroxyheptanoyl-alanyl-proline; D000626:Aminopeptidases