Synthesis and biological evaluation of constrained analogues of the opioid peptide H-Tyr-D-Ala-Phe-Gly-NH2 using the 4-amino-2-benzazepin-3-one scaffold
Synthesis and biological evaluation of constrained analogues of the opioid peptide H-Tyr-D-Ala-Phe-Gly-NH2 using the 4-amino-2-benzazepin-3-one scaffold
复制标题
DOI：
10.1111/j.1399-3011.2005.00291.x
复制
发表时间：
2005-11-01
期刊：
影响因子：
--
通讯作者：
Tourwé, D
中科院分区：
文献类型：
--
作者：
Ballet, S;Frycia, A;Tourwé, D
构象受限的二肽部分4-氨基-1，2，4，5-四氢-2-苯并氮杂庚因-3-酮（阿坝）- Gly（[（4S）-氨基-3-氧代-1，2，4，5-四氢-1H-2-苯并氮杂庚因-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-Ala（[（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）是基于使用恶唑烷酮作为N-酰基环丙烷前体的合成策略.将这些阿坝支架引入皮吗啡肽的N-末端四肽（H-Tyr-（D）-Ala-Phe-Gly-Tyr-Pro-Ser-NH 2）中诱导了对阿片样物质μ-和δ-受体的亲和力和选择性的显著变化。本文报道了皮吗啡肽N-末端四肽H-Tyr-（D）-AlaPhe-Gly-NH 2的缩窄类似物的合成及其体内外生物学评价.
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- 2benzazepin- 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)- AlaPhe- Gly- NH2, which is the minimal subunit of dermorphin needed for dermorphin- like opiate activity.