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- W2894838698 abstract "Abstract The impact that β-arrestin proteins have on G-protein-coupled receptor trafficking, signaling and physiological behavior has gained much appreciation over the past decade. A number of studies have attributed the side effects associated with the use of naturally occurring and synthetic opioids, such as respiratory depression and constipation, to excessive recruitment of β-arrestin. These findings have led to the development of biased opioid small molecule agonists that do not recruit β-arrestin, activating only the canonical G-protein pathway. Similar G-protein biased small molecule opioids have been found to occur in nature, particularly within kratom, and opioids within salvia have served as a template for the synthesis of other G-protein-biased opioids. Here, we present the first report of naturally occurring peptides that selectively activate G-protein signaling pathways with minimal β-arrestin recruitment. We find that rubiscolin peptides, which are produced as cleavage products of the plant protein rubisco, bind to and activate G-protein signaling at δ opioid receptors. However, unlike the naturally occurring δ opioid peptides leu-enkephalin and deltorphin II, the rubiscolin peptides only very weakly recruit β-arrestin 2 and have undectable recruitment of β-arrestin 1 at the δ opioid receptor." @default.
- W2894838698 created "2018-10-12" @default.
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- W2894838698 date "2018-10-02" @default.
- W2894838698 modified "2023-09-27" @default.
- W2894838698 title "Rubsicolins are naturally occurring G-protein-biased delta opioid receptor peptides" @default.
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- W2894838698 doi "https://doi.org/10.1101/433805" @default.
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