AI Article Synopsis
- - This study focuses on developing new analogues of endomorphin-2 by replacing specific amino acids (Phe(3) and Phe(4)) with unnatural β-amino acids to enhance their opioid binding affinity.
- - Ligand-stimulated binding assays showed that some of these analogues maintained strong affinity, particularly for the δ receptor, suggesting potential therapeutic uses.
- - Techniques like (1)H NMR and molecular docking were used to analyze the compounds, revealing that they mostly adopt bent structures and sharing a common binding mode at the μ-opioid receptor, which helps explain their effectiveness.
Article 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(4)residues. 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. (1)H 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.
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| http://dx.doi.org/10.1007/s11030-012-9399-5 | DOI Listing |
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