dc.contributor.author | Conole, D | en_US |
dc.contributor.author | Myers, SH | en_US |
dc.contributor.author | Mota, F | en_US |
dc.contributor.author | Hobbs, AJ | en_US |
dc.contributor.author | Selwood, DL | en_US |
dc.date.accessioned | 2018-10-04T10:31:45Z | |
dc.date.available | 2018-09-04 | en_US |
dc.date.issued | 2019-06 | en_US |
dc.date.submitted | 2018-09-28T08:58:36.163Z | |
dc.identifier.other | 10.1111/cbdd.13395 | |
dc.identifier.uri | https://onlinelibrary.wiley.com/doi/abs/10.1111/cbdd.13395 | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/45923 | |
dc.description | This is the peer reviewed version of the following article:Conole, D., et al. "Biophysical screening methods for extracellular domain peptide receptors, application to natriuretic peptide receptor C ligands." Chemical Biology and Drug Design 0(ja)., which has been published in final form at [https://doi.org/10.1111/cbdd.13395. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions | en_US |
dc.description.abstract | Endothelium-derived C-type natriuretic peptide possesses cytoprotective and anti-atherogenic functions that regulate vascular homeostasis. The vasoprotective effects of C-type natriuretic peptide are somewhat mediated by the natriuretic peptide receptor C, suggesting that this receptor represents a novel therapeutic target for the treatment of cardiovascular diseases. In order to facilitate our drug discovery efforts, we have optimized an array of biophysical methods including surface plasmon resonance, fluorescence polarization and thermal shift assays to aid in the design, assessment and characterization of small molecule agonist interactions with natriuretic peptide receptors. Assay conditions are investigated to explore the feasibility and dynamic range of each method, and peptide-based agonists and antagonists are used as controls to validate these conditions. Once established, each technique was compared and contrasted with respect to their drug discovery utility. We foresee that such techniques will facilitate the discovery and development of potential therapeutic agents for NPR-C and other large extracellular domain membrane receptors. | en_US |
dc.description.sponsorship | This work was funded by a translational award from the British Heart Foundation(TG/15/3/31692), Wellcome Trust grants (084449/Z/07/Z and 078496/Z/05/Z), UCL Business PLC (PoC-12-007)and an Apollo Therapeutics one-off experiment fund | en_US |
dc.format.extent | 1011 - 1020 | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Chem Biol Drug Des | en_US |
dc.rights | All rights reserved | |
dc.subject | CNP | en_US |
dc.subject | NPR-C | en_US |
dc.subject | biophysical | en_US |
dc.subject | fluorescence polarization | en_US |
dc.subject | surface plasmon resonance | en_US |
dc.subject | thermal shift | en_US |
dc.title | Biophysical screening methods for extracellular domain peptide receptors, application to natriuretic peptide receptor C ligands. | en_US |
dc.type | Article | |
dc.rights.holder | John Wiley & Sons, Inc. | |
dc.identifier.doi | 10.1111/cbdd.13395 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/30218492 | en_US |
pubs.issue | 6 | en_US |
pubs.notes | No embargo | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 93 | en_US |
dcterms.dateAccepted | 2018-09-04 | en_US |
qmul.funder | Lead optimisation of novel small molecule natriuretic receptor (NPR)-C agonists for the treatment of myocardial infarction::British Heart Foundation | en_US |
qmul.funder | Lead optimisation of novel small molecule natriuretic receptor (NPR)-C agonists for the treatment of myocardial infarction::British Heart Foundation | en_US |
qmul.funder | Lead optimisation of novel small molecule natriuretic receptor (NPR)-C agonists for the treatment of myocardial infarction::British Heart Foundation | en_US |