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

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 ?-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.

SUBMITTER: Stefanucci A

PROVIDER: S-EPMC6453917 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Stefanucci Azzurra A Lei Wei W Pieretti Stefano S Novellino Ettore E Dimmito Marilisa Pia MP Marzoli Francesca F Streicher John M JM Mollica Adriano A

Scientific reports 20190408 1

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 w ...[more]

PMID: 30962495

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