Structural comparison of endomorphin-2 and its conformationally restricted analog |
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Authors: | Attila Borics Katarzyna Gach Jakub Fichna Dariusz Sobolewski Géza Toth Anna Janecka |
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Institution: | 1.Institute of Biochemistry,Biological Research Center of the Hungarian Academy of Sciences,Szeged,Hungary;2.Department of Biomolecular Chemistry,Medical University,Lodz,Poland;3.Faculty of Chemistry,Gdansk University,Gdansk,Poland |
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Abstract: | In the present study, the effect of a conformational constraint introduced into the endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM-2) structure was studied using computational analysis and radioligand binding assay. EM-2 was modified by connecting
nitrogen atoms of both phenylalanine residues by a methylene bridge. The obtained analog did not bind to the μ- or δ-opioid
receptors in the in vitro studies. The computational analysis of this analog showed twisted, type IV turns and the absence of canonical β-turns typical
for the EM-2 structure, which can be explained by the lack of hydrogen bonds involving Phe4. Our results show that the introduction of chemical constraint in the EM-2 structure has a significant effect on opioid receptor
affinity and in vitro bioactivity. |
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