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Synthesis and evaluation of new endomorphin-2 analogues containing (Z)-alpha,beta-didehydrophenylalanine (Delta(Z)Phe) residues.

ABSTRACT: New endomorphin-2 (EM-2) analogues incorporating (Z)-alpha,beta-didehydrophenylalanine (Delta(Z)Phe) in place of the native phenylalanine in EM-2 are reported. Tyr-Pro-Delta(Z)Phe-Phe-NH(2) {[Delta(Z)Phe(3)]EM-2} (1), Tyr-Pro-Phe-Delta(Z)Phe-NH(2) {[Delta(Z)Phe(4)]EM-2} (2), and Tyr-Pro-Delta(Z)Phe-Delta(Z)Phe-NH(2) {[Delta(Z)Phe(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 mu opioid receptor selectivity and mu agonist activity comparable to those of the native peptide. The conformation adopted in solution and in the crystal by N-Boc-Tyr-Pro-Delta(Z)Phe-Phe-NH(2) (8) is reported.

SUBMITTER: Torino D

PROVIDER: S-EPMC2918392 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Synthesis and evaluation of new endomorphin-2 analogues containing (Z)-alpha,beta-didehydrophenylalanine (Delta(Z)Phe) residues.

Torino Domenica D Mollica Adriano A Pinnen Francesco F Feliciani Federica F Lucente Gino G Fabrizi Giancarlo G Portalone Gustavo G Davis Peg P Lai Josephine J Ma Shou-Wu SW Porreca Frank F Hruby Victor J VJ

Journal of medicinal chemistry 20100601 11

New endomorphin-2 (EM-2) analogues incorporating (Z)-alpha,beta-didehydrophenylalanine (Delta(Z)Phe) in place of the native phenylalanine in EM-2 are reported. Tyr-Pro-Delta(Z)Phe-Phe-NH(2) {[Delta(Z)Phe(3)]EM-2} (1), Tyr-Pro-Phe-Delta(Z)Phe-NH(2) {[Delta(Z)Phe(4)]EM-2} (2), and Tyr-Pro-Delta(Z)Phe-Delta(Z)Phe-NH(2) {[Delta(Z)Phe(3,4)]EM-2}(3) have been synthesized, their opioid receptor binding affinities and tissue bioassay activities were determined, and their conformational properties were e ...[more]

PMID: 20476738

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