Cai Yunxin, Lu Dandan, Chen Zhen, Ding Yi, Chung Nga N, Li Tingyou, Schiller Peter W
School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China.
Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada.
Bioorg Med Chem Lett. 2016 Aug 1;26(15):3629-31. doi: 10.1016/j.bmcl.2016.06.003. Epub 2016 Jun 3.
Analogues of [Dmt(1)]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 Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment.
[Dmt(1)]DALDA（H-Dmt-d-Arg-Phe-Lys-NH2；Dmt = 2',6'-二甲基酪氨酸）是一种具有线粒体靶向抗氧化活性的强效μ阿片受体激动剂肽，通过用各种2',6'-二烷基化酪氨酸类似物取代Dmt来制备其类似物，包括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）。所有化合物均为选择性μ阿片受体激动剂，Tmt(1)-、Emt(1)和Det(1)-类似物表现出亚纳摩尔的μ阿片受体结合亲和力。在DPPH自由基清除能力测定中，Tmt(1)-和Emt(1)-类似物与Dmt(1)-母体肽相比表现出改善的抗氧化活性，因此作为治疗神经性疼痛的候选药物具有研究价值。
