Agonist vs Antagonist Behavior of δ Opioid Peptides Containing Novel Phenylalanine Analogues in Place of Tyr1
Agonist vs Antagonist Behavior of δ Opioid Peptides Containing Novel Phenylalanine Analogues in Place of Tyr1
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DOI：
10.1021/jm9004913
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发表时间：
2009-11-12
影响因子：
7.3
通讯作者：
Schiller, Peter W.
中科院分区：
文献类型：
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作者：
Berezowska, Irena;Chung, Nga N.;Schiller, Peter W.
新的苯丙氨酸类似物4 ′-[N-（（4 ′-苯基）苯乙基）甲酰氨基]苯丙氨酸（Bcp）和2 ′，6 ′-二甲基-4 ′-[N-（（4 ′-苯基）苯乙基）甲酰氨基]苯丙氨酸（Dbcp）取代δ阿片拮抗剂TIPP（H-Tyr-Tic-Phe-Phe-OH; Tic =四氢异喹啉-3-羧酸）中的Tyr（1）。出乎意料的是，[Bcp（1）]TIPP是一种有效的选择性δ阿片受体激动剂，而[Dbcp（1）]TIPP保留了高h拮抗剂活性。受体对接研究表明，两种肽的结合模式相似，除了联苯乙基部分占据不同的受体亚位点。二肽H-Dbcp-Tic-OH是一种高度选择性的δ受体拮抗剂，具有亚纳摩尔的δ受体亲和力。
The novel phenylalanine analogues 4'-[N-((4'-phenyl)phenethyl)carboxamido]phenylalanine (Bcp) and 2',6'-dimethyl-4'-[N-((4'-phenyl)phenethyl)carboxamido]phenylalanine (Dbcp) were substituted for Tyr(1) in the delta opioid antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH; Tic = tetrahydroisoquinoline-3-carboxylic acid). Unexpectedly, [Bcp(1)]TIPP was a potent, selective delta opioid agonist, whereas [Dbcp(1)]TIPP retained high h antagonist activity. Receptor docking studies indicated similar binding modes for the two peptides except for the biphenylethyl moiety which occupied distinct receptor subsites, The dipeptide H-Dbcp-Tic-OH was a highly selective d antagonist with subnanomolar delta receptor affinity.