Aminopeptidase Inhibitory Properties and Analgesic Activity of (2S,3,7-3,7-Diamino-2-hydroxy-heptanoic Acid Containing Tripeptide Analogues of the N-Terminal Tripeptide of Probestin

✍ Scribed by Rosario Herranz; Soledad Vinuesa; Concepción Pérez; M. Teresa García-López; María L. De Ceballos; Francisco M. Murillo; Joaquín Del Río

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 345 KB
• Volume: 325
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.19923250812

✦ Synopsis

2S,3R)-3,7-Diamino-2-hydroxy-heptanoyl-Leu-h-OH [(=.3R)-DAHHA-Leu-Pro-OH, 41. analogue of the N-terminal hipeptide of probatin, has been synthesized, and tested as inhibitor of AP-B, Leu-AP, AP-M, and enkephalindegrading A h , and as analgesic. In order to establish structure-activity relationships the dipeptide (=,3R)-DAHHA-Pro-OH (5) and the tripep-ti& (X,3R)-DAHHA-Ala-Pm-OH (6) we-re also prepared. Compounds 4 and 6 were potent and selective inhibitors of enkephalin-degrading APs and showed a prolonged anb'nociceptive effect. Hemmung von Aminopeptidasen und analgetische Wirkung von (a, ?Jt)-3,7-DiPmino-2-hydroxy-heptan&ure enthaltenden Tripeptidanaloga des N-terminalen Tripeptids von Probestin (2S,3R)-3,7-Diamim2-hydmxy-heptanoyl-Leu-F'~1-OH [(ZS,3R)-DAHHA-Leu-&OH, 41, ein AnaIoges des N-terminalen Tripeptids von Frobestin, wude synthetisielt und sowohl als Hemmstoff von