[Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.
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.
School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China.
Yunxin
Y
Cai
School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China.
Dandan
D
Lu
School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China.
Zhen
Z
Chen
School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China.
Yi
Y
Ding
Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada.
Nga N
NN
Chung
School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Electronic address: l_tingyou@njmu.edu.cn.
Tingyou
T
Li
Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada; Department of Pharmacology, Université de Montréal, Montréal, QC H3C 3J7, Canada. Electronic address: schillp@ircm.qc.ca.
Peter W
PW
Schiller
D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013329:Structure-Activity Relationship
C424424:2',6'-dimethyltyrosyl-arginyl-phenylalanyl-lysinamide; D009842:Oligopeptides; D017450:Receptors, Opioid, mu
Bifunctional opioid/antioxidant peptides; Neuropathic pain; Opioid activity profiles; Tyrosine analogues; [Dmt(1)]DALDA