This study reports on new pharmacologically active endomorphin-2 analogues, incorporatingβ2-hPhe,β3- hPhe and β3-hTic unnatural amino acids in the place of the Phe3–Phe4residues. 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.

Synthesis, pharmacological evaluation and conformational investigation of endomorphin-2 hybrid analogues / G. Lesma, S. Salvadori, F. Airaghi, E. Bojnik, A. Borsodi, T. Recca, A. Sacchetti, G. Balboni, A. Silvani. - In: MOLECULAR DIVERSITY. - ISSN 1381-1991. - 17:1(2013), pp. 19-31. [Epub ahead of print] [10.1007/s11030-012-9399-5]

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

G. Lesma
Primo
;
F. Airaghi;T. Recca;A. Silvani
Ultimo
2013

Abstract

This study reports on new pharmacologically active endomorphin-2 analogues, incorporatingβ2-hPhe,β3- hPhe and β3-hTic unnatural amino acids in the place of the Phe3–Phe4residues. 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.
Beta-amino acid; Endomorphin-2; Molecular docking; Molecular modelling; Opioid receptor; Peptidomimetic
Settore CHIM/06 - Chimica Organica
2013
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/213080
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