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Synthesis and biological activity of tripeptide FR113680 analogues containing unconventional amino acids
Author(s) -
Caliendo G.,
Calignano A.,
Grieco P.,
Mancuso F.,
Perisutti E.,
Santini A.,
Santagada V.
Publication year - 1995
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360360404
Subject(s) - chemistry , tripeptide , amino acid , combinatorial chemistry , stereochemistry , biochemistry
In order to further develop structure–activity relationships and to get information about the biological active conformations we synthetized analogues tripeptide to the FR 113680 [Ac‐ Thr‐ D ‐Trp(CHO)‐PheNMeBzl; Ac: acethyl], in which the phenylalanine residue was replaced by unconventional amino acids [1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid (Tic); (3aS, 7aS)‐octahydroindole‐2‐carboxylic acid (Oic); (S,S,S)‐2‐azabiciclo[3.3.0]octane‐3‐carboxylic acid (Aoc); 3‐(1′‐naphthyl) alanine (Nap) phenylglicine (Phg); thienylalanine (Thi)]. The biological activity of the peptides was performed on guinea pig ileumfar neurokinin 1 (NK‐1) and on rat colon for neurokinin 2 (NK‐2). In particular, the replacement of the Phe 3 by the Oic ( 8 a ) gave an higher antagonist activity in both NK‐1 and NK‐2 receptors, but no improvement in selectivity with respect to reference tripeptide (FR113680) The compound ( 8 a ) represent the first example of highly potent peptides that do not contain an aromatic mi no acid of the third position as had been previously considered essential. © 1995 John Wiley & Sons, Inc.