Ballet S, Frycia A, Piron J, Chung N N, Schiller P W, Kosson P, Lipkowski A W, Tourwé D
Department of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium.
J Pept Res. 2005 Nov;66(5):222-30. doi: 10.1111/j.1399-3011.2005.00291.x.
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.
构象受限二肽部分4-氨基-1,2,4,5-四氢-2-苯并氮杂卓-3-酮（Aba）-甘氨酸（[(4S)-氨基-3-氧代-1,2,4,5-四氢-1H-2-苯并氮杂卓-2-基]-乙酸）和8-羟基-4-氨基-1,2,4,5-四氢-2-苯并氮杂卓-3-酮（Hba）-D-丙氨酸（[(4S)-氨基-8-羟基-3-氧代-1,2,4,5-四氢-苯并[c]氮杂卓-2-基]-丙酸）的合成基于一种使用恶唑烷酮作为N-酰基亚胺离子前体的合成策略。将这些Aba支架引入到强啡肽（H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2）的N端四肽中，导致其对阿片μ和δ受体的亲和力和选择性发生显著变化。本文提供了N端四肽H-Tyr-D-Ala-Phe-Gly-NH2的缩合类似物的合成及其体外和体内生物学评价，该四肽是具有强啡肽样阿片活性所需的强啡肽最小亚基。
