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Novel approaches leading towards peptide GPCR de‐orphanisation

The discovery of novel ligands for orphan GPCRs has profoundly affected our understanding of human biology, opening new opportunities for research, and ultimately for therapeutic development. Accordingly, much effort has been directed towards the remaining orphan receptors, yet the rate of GPCR de‐o...

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Autores principales: Hauser, Alexander S., Gloriam, David E., Bräuner‐Osborne, Hans, Foster, Simon R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042120/
https://www.ncbi.nlm.nih.gov/pubmed/31863461
http://dx.doi.org/10.1111/bph.14950
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author Hauser, Alexander S.
Gloriam, David E.
Bräuner‐Osborne, Hans
Foster, Simon R.
author_facet Hauser, Alexander S.
Gloriam, David E.
Bräuner‐Osborne, Hans
Foster, Simon R.
author_sort Hauser, Alexander S.
collection PubMed
description The discovery of novel ligands for orphan GPCRs has profoundly affected our understanding of human biology, opening new opportunities for research, and ultimately for therapeutic development. Accordingly, much effort has been directed towards the remaining orphan receptors, yet the rate of GPCR de‐orphanisation has slowed in recent years. Here, we briefly review contemporary methodologies of de‐orphanisation and then highlight our recent integrated computational and experimental approach for discovery of novel peptide ligands for orphan GPCRs. We identified putative endogenous peptide ligands and found peptide receptor sequence and structural characteristics present in selected orphan receptors. With comprehensive pharmacological screening using three complementary assays, we discovered novel pairings of 17 peptides with five different orphan GPCRs and revealed potential additional ligands for nine peptide GPCRs. These promising findings lay the foundation for future studies on these peptides and receptors to characterise their roles in human physiology and disease.
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spelling pubmed-70421202020-03-03 Novel approaches leading towards peptide GPCR de‐orphanisation Hauser, Alexander S. Gloriam, David E. Bräuner‐Osborne, Hans Foster, Simon R. Br J Pharmacol Mini‐reviews The discovery of novel ligands for orphan GPCRs has profoundly affected our understanding of human biology, opening new opportunities for research, and ultimately for therapeutic development. Accordingly, much effort has been directed towards the remaining orphan receptors, yet the rate of GPCR de‐orphanisation has slowed in recent years. Here, we briefly review contemporary methodologies of de‐orphanisation and then highlight our recent integrated computational and experimental approach for discovery of novel peptide ligands for orphan GPCRs. We identified putative endogenous peptide ligands and found peptide receptor sequence and structural characteristics present in selected orphan receptors. With comprehensive pharmacological screening using three complementary assays, we discovered novel pairings of 17 peptides with five different orphan GPCRs and revealed potential additional ligands for nine peptide GPCRs. These promising findings lay the foundation for future studies on these peptides and receptors to characterise their roles in human physiology and disease. John Wiley and Sons Inc. 2020-02-03 2020-03 /pmc/articles/PMC7042120/ /pubmed/31863461 http://dx.doi.org/10.1111/bph.14950 Text en © 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Mini‐reviews
Hauser, Alexander S.
Gloriam, David E.
Bräuner‐Osborne, Hans
Foster, Simon R.
Novel approaches leading towards peptide GPCR de‐orphanisation
title Novel approaches leading towards peptide GPCR de‐orphanisation
title_full Novel approaches leading towards peptide GPCR de‐orphanisation
title_fullStr Novel approaches leading towards peptide GPCR de‐orphanisation
title_full_unstemmed Novel approaches leading towards peptide GPCR de‐orphanisation
title_short Novel approaches leading towards peptide GPCR de‐orphanisation
title_sort novel approaches leading towards peptide gpcr de‐orphanisation
topic Mini‐reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042120/
https://www.ncbi.nlm.nih.gov/pubmed/31863461
http://dx.doi.org/10.1111/bph.14950
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