[Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.
[Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.
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[DMT（1）] Dalda类似物在位置1处用酪氨酸类似物修饰。
DOI：
10.1016/j.bmcl.2016.06.003
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发表时间：
2016-08-01
影响因子：
2.7
通讯作者：
Schiller PW
中科院分区：
文献类型：
--
作者：
Cai Y;Lu D;Chen Z;Ding Y;Chung NN;Li T;Schiller PW
[Dmt 1]DALDA的类似物以2′，6 ′-二烷基化酪氨酸（Tyr）类似物2′，4 ′，6 ′-三甲基酪氨酸（Tmt）、2′-乙基-6 ′-甲基酪氨酸（Emt）、2′-异丙基-6 ′-甲基酪氨酸（Imt）和2′，6 ′-二乙基酪氨酸（Det）取代Dmt，合成了一种具有抗氧化活性的μ阿片激动肽（H-Dmt-d-Arg-Phe-Lys-NH 2; Dmt = 2′，6 ′-二甲基酪氨酸）。所有化合物均为μ阿片受体选择性激动剂，其中Tmt 1-、Emt 1和Det 1-类似物显示出亚纳摩尔μ阿片受体结合亲和力。的TMT 1-和EMT 1-类似物显示出改善的抗氧化活性相比，DMT 1-母体肽的DPPH自由基清除能力测定，因此作为候选药物的神经性疼痛治疗的兴趣。
Analogues of [Dmt1]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt = 2′,6′-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2′,6′-dialkylated Tyr analogues, including 2′,4′,6′-trimethyltyrosine (Tmt), 2′-ethyl-6′-methyltyrosine (Emt), 2′-isopropyl-6′-methyltyrosine (Imt) and 2′,6′-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt1-, Emt1 and Det1-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt1- and Emt1-analogues showed improved antioxidant activity compared to the Dmt1-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment.