Endomorphin-2 with a beta turn backbone constraint retains the potent mu-opioid receptor agonist properties Vrije Universiteit Brussel
The constitutional similarity with different secondary structure preference between the Aba-Gly and the spiro-Aba-Gly scaffolds were exploited to design the novel endomorphin-2 analogs Tyr-spiro-(R/S)-Aba-Gly-Phe-NH2 and Tyr-(R/S)-Aba-Gly-Phe-NH2. The (R)-spiro analog was found to be a potent and selective ?-opioid agonist/partial agonist (Kiµ = 29.3 nM, IC50 = 50 nM, Ke = 0.57). NMR expts. and mol. modeling indicated that its backbone adopts ...