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[Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.

ABSTRACT: Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent ? 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 ? opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar ? 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.

SUBMITTER: Cai Y

PROVIDER: S-EPMC4955775 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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[Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.

Cai Yunxin Y Lu Dandan D Chen Zhen Z Ding Yi Y Chung Nga N NN Li Tingyou T Schiller Peter W PW

Bioorganic & medicinal chemistry letters 20160603 15

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 ...[more]

PMID: 27301366

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