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Synthesis and Opiate Activity in vitro of Five New p ‐Nitrophenylalanine 4 ‐Enkephalin‐like Peptides
Author(s) -
Fauchère JeanLuc,
Pfenninger Susanne,
Do Kim Quang,
Lemieux Carole,
Schiller Peter W.
Publication year - 1983
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19830660408
Subject(s) - chemistry , stereochemistry , opiate , serine , enkephalin , bioassay , threonine , phenylalanine , in vitro , alanine , structure–activity relationship , selectivity , receptor , peptide , biochemistry , amino acid , opioid , phosphorylation , biology , genetics , catalysis
Abstract Converging data obtained in biochemical and pharmacological bioassays for opiate activity are presented for five new enkephalin‐like peptides. The main structural features of the analogues, the synthesis of which is described in detail, were the presence of D ‐alanine or D ‐serine in position 2, p ‐nitrophenylalanine in position 4 and of a free C ‐terminal carboxylic function. Confirming our previous observations [1], the substitution of phenylalanine by p ‐nitrophenylalanine enhanced the overall opiate activity but decreased the selectivity towards m̈/δ‐receptor sites. Tyrosyl‐ D ‐alanyl‐glycyl‐ p ‐nitrophenylalanyl‐adamantylalanine was particularly potent in all assays while tyrosyl‐ D ‐seryl‐glycyl‐ p ‐nitrophenylalanyl‐leucyl‐threonine was very selective in the bioassays on isolated tissues and moderately selective in the binding assay. These results will have to be taken into account in future photoaffinity labelling and quantitative structure‐activity relationships (QSAR) studies.