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.

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

Stefanucci A.;Dimmito M. P.;Mollica A.
2019

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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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11564/717649
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