Structural comparison of endomorphin-2 and its conformationally restricted analog

• Authors: Attila Borics , Katarzyna Gach , Jakub Fichna , Dariusz Sobolewski , Géza Toth , Anna Janecka
• Languages of publication: EN

Abstracts

EN

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.

Keywords

EN

Conformational constraint; Endomorphin-2; Hydrogen bond; µ-opioid receptor ligand; Structure-activity relationship study

• Publisher: De Gruyter Open
• Journal: Open Chemistry
• Year: 2012
• Volume: 10
• Issue: 1
• Pages: 172-179

Dates

published

1 - 2 - 2012

online

24 - 11 - 2011

Contributors

author

Attila Borics

• Biological Research Center of the Hungarian Academy of Sciences

author

Katarzyna Gach

• Medical University

author

Jakub Fichna

• Medical University

author

Dariusz Sobolewski

• Gdansk University

author

Géza Toth

• Biological Research Center of the Hungarian Academy of Sciences

author

Anna Janecka

• Medical University

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Identifiers

DOI

10.2478/s11532-011-0119-2