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Genome Mining-Based Discovery of Blenny Fish-Derived Peptides Targeting the Mouse κ-Opioid Receptor. | LitMetric

AI Article Synopsis

  • Peptides are gaining attention for drug discovery targeting G protein-coupled receptors (GPCRs) due to their unique advantages over small molecules and antibodies, such as lower toxicity and higher selectivity.
  • The κ-opioid receptor (KOR) is a key target for developing safer pain relief medications, and recent findings suggest peptides can be effective analgesic candidates with fewer side effects.
  • Researchers utilized genome mining to discover new peptide ligands from blenny fish, called blenniorphins, which show strong binding and activation of KOR, highlighting the potential of these fish as a novel source for KOR-targeted therapies.*

Article Abstract

Over the past years, peptides have attracted increasing interest for G protein-coupled receptor (GPCR) drug discovery and development. Peptides occupy a unique chemical space that is not easily accessible for small molecules and antibodies and provide advantages over these ligand classes such as lower toxicity and higher selectivity. The κ-opioid receptor (KOR) is a prototypic GPCR and an appealing therapeutic target for the development of safer and more effective analgesics. Recently, peptides have emerged as analgesic drug candidates with improved side effect profiles. We have previously identified plant-derived peptides, which activate KOR. Based on this precedent, here we relied on publicly available databases to discover novel KOR peptide ligands by genome mining. Using human preprodynorphin as a query, we identified blenny fish-derived peptides, referred to as blenniorphins, capable of binding to and activating KOR with nanomolar affinity and potency, respectively. Additionally, the blenniorphins altered β-arrestin-2 recruitment at the KOR. Our study demonstrates the utility of genome mining to identify peptide GPCR ligands with intriguing pharmacological properties and unveils the potential of blenny fishes as a source for novel KOR ligands.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569185PMC
http://dx.doi.org/10.3389/fphar.2021.773029DOI Listing

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