Synthesis and biological activity of N-methylated analogs of endomorphin-2.
In this paper, we describe the synthesis of a series of endomorphin-2 analogs containing N-methylated amino acids, consecutively in each position. The mu-opioid receptor binding affinities of the new analogs were determined in the displacement experiments. Their in vivo antinociceptive activity was assessed in the hot-plate test in mice after central (icv) and peripheral (ip) administration. [Sar2]endomorphin-2, which had the highest mu-receptor affinity, also showed the strongest analgesic effect when administered centrally and was the only analog that retained activity after peripheral injection.
Kruszynski
Rafal
R
Institute of General and Ecological Chemistry, Technical University of Lodz, Lodz, Poland.
Fichna
Jakub
J
do-Rego
Jean-Claude
JC
Janecki
Tomasz
T
Kosson
Piotr
P
Pakulska
Wanda
W
Costentin
Jean
J
Janecka
Anna
A
D000818:Animals; D008297:Male; D008745:Methylation; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement; D013329:Structure-Activity Relationship
D009842:Oligopeptides; C105294:endomorphin 2