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

Azzurra Stefanucci; Wei Lei; Stefano Pieretti; Ettore Novellino; Marilisa Pia Dimmito; Francesca Marzoli; John M. Streicher; Adriano Mollica

doi:10.1038/s41598-019-42289-5

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

Azzurra Stefanucci, Wei Lei, Stefano Pieretti, Ettore Novellino, Marilisa Pia Dimmito, Francesca Marzoli, John M. Streicher, Adriano Mollica

Pharmacology

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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 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.

Original language	English (US)
Article number	5771
Journal	Scientific reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-42289-5
State	Published - Dec 1 2019

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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 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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AU - Stefanucci, Azzurra

AU - Lei, Wei

AU - Pieretti, Stefano

AU - Novellino, Ettore

AU - Dimmito, Marilisa Pia

AU - Marzoli, Francesca

AU - Streicher, John M.

AU - Mollica, Adriano

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

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