Synthesis and antinociceptive activity of peptides related to interleukin-1β193–195 Lys-Pro-Thr

Caliendo, G., Greco, G., Grieco, P., Perissutti, E., Santagada, V., Ialenti, A., Maffia, P. , Albrizio, S. and Santini, A. (1996) Synthesis and antinociceptive activity of peptides related to interleukin-1β193–195 Lys-Pro-Thr. Biopolymers, 40(5), pp. 479-484. (doi: 10.1002/(SICI)1097-0282(1996)40:5<479::AID-BIP5>3.0.CO;2-T) (PMID:9062070)

Abstract

To obtain information about the structure-activity relationships of analgesic peptides, we modified the previously reported tripeptide, H-Lys-Pro-Thr-OH (C). The proline part in C was replaced with various analogues of unconventional amino acids {(3aS, 7aS)-octahydroindole-2-carboxylic acid (Oic), (S,S,S,)-2-azabiciclo [3.3.0] octane-3-carboxylic acid (Aoc), D-Aoc, and (2S, 4R)-hydroxyproline (Hyp)} with varying lipophilic, steric, and conformational properties, and alternatively with Lys and Orn in the lysine part. Moreover, the threonine part was changed to various natural amino acids (Ser, Thr, Val, Leu). All the compounds were screened in vivo for their analgesic effects in mouse writhing test. Compound 24 (H-Orn-Hyp-Val-OH), the most active compound within the series, showed an ED50 value of 10 mg/kg, which is comparable with the ED50 values exhibited by indometacin (4.1 mg/kg) and the dipeptide H-Lys-D-Pro-OH (6.9 mg/kg), both used as reference drugs.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maffia, Professor Pasquale
• Authors: Caliendo, G., Greco, G., Grieco, P., Perissutti, E., Santagada, V., Ialenti, A., Maffia, P., Albrizio, S., and Santini, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Biopolymers
• Publisher: John Wiley & Sons, Inc.
• ISSN: 0006-3525
• ISSN (Online): 1097-0282