2005•Journal of Peptide ResearchRequires access
Synthesis and biological evaluation of constrained analogues of the opioid peptide H‐Tyr‐ d ‐Ala‐Phe‐Gly‐NH 2 using the 4‐amino‐2‐benzazepin‐3‐one scaffold
Steven Ballet, Anne Frycia, J. Piron, Nga N. Chung, Peter W. Schiller, Piotr Kossoń, Andrzej Wojciech Lipkowski, Dirk Tourwé
Open publisher page 36 citations
Abstract
The synthesis of conformationally restricted dipeptidic moieties 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba)-Gly ([(4S)-amino-3-oxo-1,2,4,5-tetrahydro-1H-2-benzazepin-2-yl]-acetic acid) and 8-hydroxy-4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Hba)-D-Ala ([(4S)-amino-8-hydroxy-3-oxo-1,2,4,5-tetrahydro-benzo[c]azepin-2-yl]-propionic acid) was based on a synthetic strategy that uses an oxazolidinone as an N-acyliminium precursor. Introducing these Aba scaffolds into the N-terminal tetrapeptide of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2)-induced remarkable shifts in affinity and selectivity towards the opioid mu- and delta-receptors. This paper provides the synthesis and biological in vitro and in vivo evaluation of constricted analogues of the N-terminal tetrapeptide H-Tyr-D-Ala-Phe-Gly-NH2, which is the minimal subunit of dermorphin needed for dermorphin-like opiate activity.