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

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 Cu(I)-catalyzed azide-alkyne cycloaddition, with the aim of improving in vivo analgesic efficacy versus DPDPE. NOVA2 showe...

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Autores principales: Stefanucci, Azzurra, Lei, Wei, Pieretti, Stefano, Novellino, Ettore, Dimmito, Marilisa Pia, Marzoli, Francesca, Streicher, John M., Mollica, Adriano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453917/
https://www.ncbi.nlm.nih.gov/pubmed/30962495
http://dx.doi.org/10.1038/s41598-019-42289-5
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author Stefanucci, Azzurra
Lei, Wei
Pieretti, Stefano
Novellino, Ettore
Dimmito, Marilisa Pia
Marzoli, Francesca
Streicher, John M.
Mollica, Adriano
author_facet Stefanucci, Azzurra
Lei, Wei
Pieretti, Stefano
Novellino, Ettore
Dimmito, Marilisa Pia
Marzoli, Francesca
Streicher, John M.
Mollica, Adriano
author_sort Stefanucci, Azzurra
collection PubMed
description 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 Cu(I)-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 (K(I) of 59.2 nM, EC(50) of 12.9 nM, E(Max) of 87.3%), and long lasting anti-nociceptive effects in mice when compared to DPDPE.
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spelling pubmed-64539172019-04-12 On resin click-chemistry-mediated synthesis of novel enkephalin analogues with potent anti-nociceptive activity Stefanucci, Azzurra Lei, Wei Pieretti, Stefano Novellino, Ettore Dimmito, Marilisa Pia Marzoli, Francesca Streicher, John M. Mollica, Adriano Sci Rep Article 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 Cu(I)-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 (K(I) of 59.2 nM, EC(50) of 12.9 nM, E(Max) of 87.3%), and long lasting anti-nociceptive effects in mice when compared to DPDPE. Nature Publishing Group UK 2019-04-08 /pmc/articles/PMC6453917/ /pubmed/30962495 http://dx.doi.org/10.1038/s41598-019-42289-5 Text en © 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. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Stefanucci, Azzurra
Lei, Wei
Pieretti, Stefano
Novellino, Ettore
Dimmito, Marilisa Pia
Marzoli, Francesca
Streicher, John M.
Mollica, Adriano
On resin click-chemistry-mediated synthesis of novel enkephalin analogues with potent anti-nociceptive activity
title On resin click-chemistry-mediated synthesis of novel enkephalin analogues with potent anti-nociceptive activity
title_full On resin click-chemistry-mediated synthesis of novel enkephalin analogues with potent anti-nociceptive activity
title_fullStr On resin click-chemistry-mediated synthesis of novel enkephalin analogues with potent anti-nociceptive activity
title_full_unstemmed On resin click-chemistry-mediated synthesis of novel enkephalin analogues with potent anti-nociceptive activity
title_short On resin click-chemistry-mediated synthesis of novel enkephalin analogues with potent anti-nociceptive activity
title_sort on resin click-chemistry-mediated synthesis of novel enkephalin analogues with potent anti-nociceptive activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453917/
https://www.ncbi.nlm.nih.gov/pubmed/30962495
http://dx.doi.org/10.1038/s41598-019-42289-5
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