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Synthesis and antinociceptive activity of peptides related to interleukin‐1β 193–195 Lys‐Pro‐Thr
Author(s) -
Caliendo G.,
Greco G.,
Grieco P.,
Perissutti E.,
Santagada V.,
Ialenti A.,
Maffia P.,
Albrizio S.,
Santini A.
Publication year - 1996
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(1996)40:5<479::aid-bip5>3.0.co;2-t
Subject(s) - chemistry , dipeptide , stereochemistry , tripeptide , ed50 , analgesic , in vivo , proline , peptide , steric effects , amino acid , in vitro , biochemistry , pharmacology , medicine , microbiology and biotechnology , biology
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 ED 50 value of 10 mg/kg, which is comparable with the ED 50 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. © 1997 John Wiley & Son's, Inc. Biopoly 40: 479–484, 1996