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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics / chemical synthesis*
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Analgesics / pharmacology
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Animals
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CHO Cells
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Click Chemistry / methods*
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Cricetinae
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Cricetulus
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Cycloaddition Reaction / methods
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Enkephalin, D-Penicillamine (2,5)- / analogs & derivatives*
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Enkephalin, D-Penicillamine (2,5)- / chemical synthesis
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Enkephalin, D-Penicillamine (2,5)- / pharmacology
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Humans
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Male
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Mice
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Protein Binding
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Receptors, Opioid, mu / metabolism
Substances
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Analgesics
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Receptors, Opioid, mu
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Enkephalin, D-Penicillamine (2,5)-