Abstract
The tetrapeptide DALDA (H-Tyr- d-Arg-Phe-Lys-NH 2) 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 Tyr 1, or Orn or α,γ-diaminobutyric acid (A 2bu) in place of Lys 4, were synthesized. All compounds displayed high μ 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 [Dmt 1]DALDA showing the highest potency. Because of its extraordinary μ agonist potency, high μ selectivity, polar character (charge of 3+) and metabolic stability, [Dmt 1]DALDA has potential for use in obstetrical or peripheral analgesia.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
