Synthesis and evaluation of new endomorphin-2 analogues containing (Z)-α,β-didehydrophenylalanine (δZPhe) residues

Domenica Torino, Adriano Mollica, Francesco Pinnen, Federica Feliciani, Gino Lucente, Giancarlo Fabrizi, Gustavo Portalone, Peg Davis, Josephine Lai, Shou Wu Ma, Frank Porreca, Victor J. Hruby

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31 Scopus citations

Abstract

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-NH 2 {[δZPhe3]EM-2} (1), Tyr-Pro-Phe-δZPhe-NH2 {[δZPhe 4]EM-2} (2), and Tyr-Pro-δZPhe- δZPhe-NH2 {[δZPhe 3,4]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.

Original languageEnglish (US)
Pages (from-to)4550-4554
Number of pages5
JournalJournal of Medicinal Chemistry
Volume53
Issue number11
DOIs
StatePublished - Jun 10 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Torino, D., Mollica, A., Pinnen, F., Feliciani, F., Lucente, G., Fabrizi, G., Portalone, G., Davis, P., Lai, J., Ma, S. W., Porreca, F., & Hruby, V. J. (2010). Synthesis and evaluation of new endomorphin-2 analogues containing (Z)-α,β-didehydrophenylalanine (δZPhe) residues. Journal of Medicinal Chemistry, 53(11), 4550-4554. https://doi.org/10.1021/jm1001343