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- Title
The Biological Consequences of Replacing d-Ala in Biphalin with Amphiphilic α-Alkylserines.
- Authors
Frączak, Oliwia; Lasota, Anika; Leśniak, Anna; Lipkowski, Andrzej W.; Olma, Aleksandra
- Abstract
Biphalin, a synthetic opioid peptide with a broad affinity for all opioid receptors (δ, μ, and κ) and high antinociceptive activity, has been under extensive study as a potential analgesic drug. This study presents the synthesis and biological properties of four new analogues of biphalin containing amphiphilic α-alkylserines in position 2 and 2′. The incorporation of bulky α,α-disubstituted amino acids in the peptide chain using standard peptide chemistry is often unsuccessful. We synthesized depsipeptides, and then, the desired peptides were obtained by internal O, N-migration of the acyl residue from the hydroxyl to the amino group under mild basic conditions. The potency and selectivity of the new analogues were evaluated by a competitive receptor-binding assay in the rat brain using [3H]DAMGO (a μ ligand) and [3H]DELT (a δ ligand). Their binding affinity is strongly dependent on the chirality of α-alkylserine, as analogues containing ( R)-α-alkylserines displayed higher μ receptor affinity and selectivity than those incorporating the ( S)-isomers.
- Subjects
OPIOID peptides; DEPSIPEPTIDES; AMINO group; AMPHIPHILES; RADIOLIGAND assay; SERINE
- Publication
Chemical Biology & Drug Design, 2014, Vol 84, Issue 2, p199
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.12305