On resin click-chemistry-mediated synthesis of novel enkephalin analogues with potent anti-nociceptive activity

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Author
Stefanucci, Azzurra
Lei, Wei
Pieretti, Stefano
Novellino, Ettore
Dimmito, Marilisa Pia
Marzoli, Francesca
Streicher, John M
Mollica, Adriano
Affiliation
Univ Arizona, Coll Med, Dept Pharmacol
Issue Date
2019-04-08

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Publisher
NATURE PUBLISHING GROUP
Citation
Stefanucci, A., Lei, W., Pieretti, S., Novellino, E., Dimmito, M. P., Marzoli, F., ... & Mollica, A. (2019). On resin click-chemistry-mediated synthesis of novel enkephalin analogues with potent anti-nociceptive activity. Scientific reports, 9(1), 5771.
Journal
SCIENTIFIC REPORTS
Rights
© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
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This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
Abstract
Here, we report the chemical synthesis of two DPDPE analogues 7a (NOVA1) and 7b (NOVA2). This entailed the solid-phase synthesis of two enkephalin precursor chains followed by a CuI-catalyzed azide-alkyne cycloaddition, with the aim of improving in vivo analgesic efficacy versus DPDPE. NOVA2 showed good affinity and selectivity for the μ-opioid receptor (KI of 59.2 nM, EC50 of 12.9 nM, EMax of 87.3%), and long lasting anti-nociceptive effects in mice when compared to DPDPE.
Note
Open access journal
ISSN
2045-2322
PubMed ID
30962495
DOI
10.1038/s41598-019-42289-5
Version
Final published version
Sponsors
University of Arizona
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