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

Autor:	F. Pinnen, Federica Feliciani, Victor J. Hruby, Frank Porreca, Peg Davis, Josephine Lai, Gino Lucente, Gustavo Portalone, Adriano Mollica, Giancarlo Fabrizi, Domenica Torino, Shou Wu Ma
Rok vydání:	2010
Předmět:	chemistry.chemical_classification Agonist Oligopeptide Chemistry Stereochemistry medicine.drug_class Phenylalanine Peptide Stereoisomerism Affinities Opioid Receptor Binding Drug Discovery medicine Molecular Medicine Selectivity
Zdroj:	Journal of Medicinal Chemistry. 53:4550-4554
ISSN:	1520-4804 0022-2623
DOI:	10.1021/jm1001343
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7cb1938d5169eda03b0492a72aa1f8a3 https://doi.org/10.1021/jm1001343 Zobrazit plný text záznamu