Title: Synthesis and characterization of potent and selective mu-opioid receptor antagonists, [Dmt(1), D-2-Nal(4)]endomorphin-1 (antanal-1) and [Dmt(1), D-2-Nal(4)]endomorphin-2 (antanal-2)
Authors: Fichna, Jakub ×
do-Rego, Jean-Claude
Chung, Nga N
Lemieux, Carole
Schiller, Peter W
Poels, Jeroen
Vanden Broeck, Jozef
Costentin, Jean
Janecka, Anna #
Issue Date: Feb-2007
Publisher: Amer chemical soc
Series Title: Journal of Medicinal Chemistry vol:50 issue:3 pages:512-520
Abstract: To synthesize potent antagonists of the mu-opioid receptor, we prepared a series of endomorphin-1 and endomorphin-2 analogues with 3-(1-naphthyl)-D-alanine (D-1-Nal) or 3-(2-naphthyl)-D-alanine (D-2-Nal) in position 4. Some of these analogues displayed weak antagonist properties. We tried to strengthen these properties by introducing the structurally modified tyrosine residue 2,6-dimethyltyrosine (Dmt) in place of Tyr(1). Among the synthesized compounds, [Dmt(1), D-2-Nal(4)]endomorphin-1, designated antanal-1, and [Dmt(1), D-2-Nal(4)]endomorphin-2, designated antanal-2, turned out to be highly potent and selective mu-opioid receptor antagonists, as judged on the basis of two functional assays, the receptor binding assay and the hot plate test of analgesia. Interestingly, another analogue of this series, [Dmt(1), D-1-Nal(4)]endomorphin-1, turned out to be a moderately potent mixed mu-agonist/delta-antagonist.
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Animal Physiology and Neurobiology Section - miscellaneous
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
Fichna et al._2007_J Medicin Chem_vol50_p512-520.pdf Published 482KbAdobe PDFView/Open Request a copy

These files are only available to some KU Leuven Association staff members


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science