Synthesis and Evaluation of New Endomorphin-2 Analogues Containing (Z)-α,β-Didehydrophenylalanine (ΔZPhe) Residues

• Published in: Journal of medicinal chemistry Vol. 53; no. 11; pp. 4550 - 4554
• Main Authors: Torino, Domenica, Mollica, Adriano, Pinnen, Francesco, Feliciani, Federica, Lucente, Gino, Fabrizi, Giancarlo, Portalone, Gustavo, Davis, Peg, Lai, Josephine, Ma, Shou-Wu, Porreca, Frank, Hruby, Victor J
• Format: Journal Article
• Language: English
• Published: American Chemical Society 10.06.2010
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm1001343

New endomorphin-2 (EM-2) analogues incorporating (Z)-α,β-didehydrophenylalanine (ΔZPhe) in place of the native phenylalanine in EM-2 are reported. Tyr-Pro-ΔZPhe-Phe-NH2 {[ΔZPhe3]EM-2} (1), Tyr-Pro-Phe-ΔZPhe-NH2 {[ΔZPhe4]EM-2} (2), and Tyr-Pro-ΔZPhe-ΔZPhe-NH2 {[ΔZPhe3,4]EM-2}(3) have been synthesized, their opioid receptor binding affinities and tissue bioassay activities were determined, and their conformational properties were examined. Compound 2 shows high μ opioid receptor selectivity and μ agonist activity comparable to those of the native peptide. The conformation adopted in solution and in the crystal by N-Boc-Tyr-Pro-ΔZPhe-Phe-NH2 (8) is reported.