Synthesis, pharmacological evaluation and conformational investigation of endomorphin-2 hybrid analogues

Lesma, Giordano and Salvadori, Severo and Airaghi, Francesco and Bojnik, Engin and Borsodi, Anna (2013) Synthesis, pharmacological evaluation and conformational investigation of endomorphin-2 hybrid analogues. MOLECULAR DIVERSITY, 17 (1). pp. 19-31. ISSN 1381-1991

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Abstract

This study reports on new pharmacologically active endomorphin-2 analogues, incorporating β 2-hPhe, β 3-hPhe and β 3-hTic unnatural amino acids in the place of the Phe 3-Phe 4residues. Such α, β-hybrid analogues were designed to exploit the great potential of β-amino acids in generating conformational variation at the key positions 3 and 4, with the aim of evaluating the effect on the opioid binding affinity. Ligand-stimulated binding assays indicated that some analogues retained a significant affinity, especially for the δ receptor. 1H NMR and molecular modelling suggested the predominance of bent structures for all compounds. The molecular docking with the μ-opioid receptor model was also performed, highlighting a common binding mode for active compounds and helping to rationalize the observed structure-activity data. © 2012 Springer Science+Business Media Dordrecht.

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