Publication
Title
Chemical space screening around in opioid peptides : modulating µ versus δ agonism by Suzuki-Miyaura cross-couplings
Author
Abstract
In this study, affinities and activities of derivatized analogues of Dmt-dermorphin[1-4] (i.e. Dmt-D-Ala-Phe-GlyNH2, Dmt = 2,6-dimethyl-(S)-tyrosine) for the µ opioid receptor (MOP) and δ opioid receptor (DOP) were evaluated using radioligand binding studies, functional cell-based assays and isolated organ bath experiments. By means of solid-phase or solution-phase Suzuki-Miyaura cross-couplings, various substituted regioisomers of the phenylalanine moiety in position 3 of the sequence were prepared. An 18-membered library of opioid tetrapeptides was generated via screening of the chemical space around the Phe3 side chain. These substitutions modulated bioactivity, receptor subtype selectivity and highly effective ligands with subnanomolar binding affinities, contributed to higher functional activities and potent analgesic actions. In search of selective peptidic ligands, we show here that the Suzuki-Miyaura reaction is a versatile and robust tool which could also be deployed elsewhere.
Language
English
Source (journal)
Bioorganic and medicinal chemistry letters. - Oxford
Bioorganic and medicinal chemistry letters. - Oxford
Publication
Oxford : 2018
ISSN
0960-894X
Volume/pages
28 :13 (2018) , p. 2320-2323
ISI
000436594200017
Pubmed ID
29853330
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 22.05.2018
Last edited 21.09.2021
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