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|Title:||Design of a stable cyclic peptide analgesic derived from sunflower seeds that targets the κ-opioid receptor for the treatment of chronic abdominal pain|
|Other Titles:||Design of a stable cyclic peptide analgesic derived from sunflower seeds that targets the kappa-opioid receptor for the treatment of chronic abdominal pain|
|Citation:||Journal of Medicinal Chemistry, 2021; 64(13):9042-9055|
|Edin Muratspahic, Nataša Tomaševic, Johannes Koehbach, Leopold Duerrauer, Seid Hadžić, Joel Castro ... et al.|
|Abstract:||The rising opioid crisis has become a worldwide societal and public health burden, resulting from the abuse of prescription opioids. Targeting the κ-opioid receptor (KOR) in the periphery has emerged as a powerful approach to develop novel pain medications without central side effects. Inspired by the traditional use of sunflower (Helianthus annuus) preparations for analgesic purposes, we developed novel stabilized KOR ligands (termed as helianorphins) by incorporating different dynorphin A sequence fragments into a cyclic sunflower peptide scaffold. As a result, helianorphin-19 selectively bound to and fully activated the KOR with nanomolar potency. Importantly, helianorphin-19 exhibited strong KOR-specific peripheral analgesic activity in a mouse model of chronic visceral pain, without inducing unwanted central effects on motor coordination/sedation. Our study provides a proof of principle that cyclic peptides from plants may be used as templates to develop potent and stable peptide analgesics applicable via enteric administration by targeting the peripheral KOR for the treatment of chronic abdominal pain.|
Mice, Inbred C57BL
Receptors, Opioid, kappa
Dose-Response Relationship, Drug
|Rights:||© 2021 The Authors. Published by American Chemical Society|
|Appears in Collections:||Aurora harvest 4|
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