97372-02-6Relevant academic research and scientific papers
Structural studies of [2′,6′-dimethyl-L-tyrosine1]endomorphin-2 analogues: Enhanced activity and cis orientation of the Dmt-Pro amide bond
Okada, Yoshio,Fujita, Yoshio,Motoyama, Takashi,Tsuda, Yuko,Yokoi, Toshio,Li, Tingyou,Sasaki, Yusuke,Ambo, Akihiro,Jinsmaa, Yunden,Bryant, Sharon D.,Lazarus, Lawrence H.
, p. 1983 - 1994 (2007/10/03)
Analogues of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) (1) were designed to examine the importance of each residue on μ-opioid receptor interaction. Replacement of Tyr1 by 2′,6′-dimethyl-L-tyrosine (Dmt) (9-12) exerted profound effects: [Dmt1]EM-2 (9) elevated μ-opioid affinity 4.6-fold (Kiμ=0.15 nM) yet selectivity fell 330-fold as δ-affinity rose (Kiδ=28.2 nM). This simultaneous increased μ- and δ-receptor bioactivities resulted in dual agonism (IC50=0.07 and 1.87 nM, respectively). While substitution of Phe4 by a phenethyl group (4) decreased μ affinity (Kiμ=13.3 nM), the same derivative containing Dmt (12) was comparable to EM-2 but also acquired weak δ antagonism (pA2=7.05). 1H NMR spectroscopy revealed a trans configuration (1:2 to 1:3, cis/trans) in the Tyr-Pro amide bond, but a cis configuration (5:3 to 13:7, cis/trans) with Dmt-Pro analogues.
