[Dmt¹]DALDA analogues modified with tyrosine analogues at position 1

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• 作者：Yunxin Cai^a ; Dandan Lu^a ; Zhen Chen^a ; Yi Ding^a ; Nga N. Chung^b ; Tingyou Li^a ; ^{l_tingyou@njmu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Peter W. Schiller^b ; ^c ; ^{schillp@ircm.qc.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BBB ; blood&ndash ; brain&ndash ; barrier ; Boc ; tert-butyloxycarbonyl ; CPIP ; chronic postischemia pain ; CRPS-I ; complex regional pain syndrome-type I ; DALDA ; H-Tyr-d-Arg-Phe-Lys-NH2 ; DAMGO ; H-Tyr-d-Ala-Gly-Phe(NMe)-Gly-ol ; Det ; 2&prime ; 6&prime ; -diethyltyrosine ; DIEA ; N ; N-diisopropylethylamine ; DIPP-NH2 ; H-Dmt-Tic-Phe-Phe-NH2 ; Dmp ; 2&prime ; 6&prime ; -dimetylphenylalanine ; Dmt ; 2&prime ; 6&prime ; -dimethyltyrosine ; [Dmt1]DALDA ; H-Dmt-d-Arg-Phe-Lys-NH2 ; DPPH ; 1 ; 1-diphenyl-2-picrylhydrazyl ; DSLET ; H-Tyr-d-
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 August 2016
• 年：2016
• 卷：26
• 期：15
• 页码：3629-3631
• 全文大小：326 K

文摘

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.