Biophysical screening methods for extracellular domain peptide receptors, application to natriuretic peptide receptor C ligands.
CNP
NPR-C
biophysical
fluorescence polarization
surface plasmon resonance
thermal shift
Journal
Chemical biology & drug design
ISSN: 1747-0285
Titre abrégé: Chem Biol Drug Des
Pays: England
ID NLM: 101262549
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
30
05
2018
revised:
15
08
2018
accepted:
04
09
2018
pubmed:
16
9
2018
medline:
6
5
2020
entrez:
16
9
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30218492
doi: 10.1111/cbdd.13395
pmc: PMC6879014
doi:
Substances chimiques
Ligands
0
Receptors, Peptide
0
Natriuretic Peptide, C-Type
127869-51-6
Banques de données
GENBANK
['NM_000908']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1011-1020Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 078496/Z/05/Z
Pays : United Kingdom
Organisme : British Heart Foundation
ID : TG/15/3/31692
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 084449/Z/07/Z
Pays : United Kingdom
Informations de copyright
© 2018 The Authors. Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.
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