326484-99-5Relevant academic research and scientific papers
Synthesis and in vitro opioid activity profiles of DALDA analogues
Schiller, Peter W.,Nguyen, Thi M.-D.,Berezowska, Irena,Dupuis, Sebastien,Weltrowska, Grazyna,Chung, Nga N.,Lemieux, Carole
, p. 895 - 901 (2007/10/03)
The tetrapeptide DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) is a polar and selective μ agonist showing poor penetration of the placental and blood-brain barriers. In an effort to enhance the potency of DALDA, analogues containing 2',6'-dimethyltyrosine (Dmt), N,2',6'-trimethyltyrosine (Tmt), 2'-methyltyrosine (Mmt) or 2'-hydroxy,6'-methyltyrosine (Hmt) in place of Tyr1, or Orn or α,γ-diaminobutyric acid (A2bu) in place of Lys4, were synthesized. All compounds displayed high it receptor selectivity in the rat and guinea pig brain membrane binding assays and most of them were more potent μ agonists than DALDA in the μ receptor-representative guinea pig ileum assay, with [Dmt1]DALDA showing the highest potency. Because of its extraordinary μ agonist potency, high μ selectivity, polar character (charge of 3 +) and metabolic stability, [Dmt1]DALDA has potential for use in obstetrical or peripheral analgesia. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
