+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

High-throughput screen for pharmacoperones of the vasopressin type 2 receptor



High-throughput screen for pharmacoperones of the vasopressin type 2 receptor



Journal of Biomolecular Screening 18(8): 930-937



Pharmacoperone drugs correct the folding of misfolded protein mutants and restore function (i.e., "rescue") by correcting the routing of (otherwise) misrouted mutants. Assays for pharmacoperones have not been applied to screen large libraries previously. Currently, most pharmacoperones possess intrinsic agonist or antagonist activities since these were identified using high-throughput screens aimed at discovering direct agonists or antagonists. Here we describe an ultra-high-throughput compatible no-wash assay system designed to specifically identify pharmacoperones of the vasopressin type 2 receptor (V2R). Development of such assays is important and novel since useful chemical structures with the ability to control cellular trafficking but lacking intrinsic agonist or antagonist properties have not likely been identified using existing screens. In the described assay, the level of functional human V2R (hV2R) (mutant) present in each test well is quantitated by stimulation with saturating levels of agonist followed by use of a luminescent-based cyclic adenosine monophosphate assay. This allows the assay to identify compounds that increase the trafficking of mutant hV2R[L(83)Q] in our model system.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 053552842

Download citation: RISBibTeXText

PMID: 23640875

DOI: 10.1177/1087057113483559


Related references

Chemical validation and optimization of pharmacoperones targeting vasopressin type 2 receptor mutant. Biochemical Journal 475(18): 2941-2953, 2018

A phenotypic high throughput screening assay for the identification of pharmacoperones for the gonadotropin releasing hormone receptor. Assay and Drug Development Technologies 12(4): 238-246, 2014

Transitioning pharmacoperones to therapeutic use: in vivo proof-of-principle and design of high throughput screens. Pharmacological Research 83: 38-51, 2014

Identification of Potential Pharmacoperones Capable of Rescuing the Functionality of Misfolded Vasopressin 2 Receptor Involved in Nephrogenic Diabetes Insipidus. Journal of Biomolecular Screening 21(8): 824-831, 2016

A quantitative high-throughput screen identifies novel inhibitors of the interaction of thyroid receptor beta with a peptide of steroid receptor coactivator 2. Journal of Biomolecular Screening 16(6): 618-627, 2011

Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen. Slas Discovery 22(3): 324-331, 2017

Development of a Whole Cell High Throughput Screen for Muscarinic Receptor Agonists. Journal of Biomolecular Screening 2(2): 79-84, 1997

Rational screen of high kelimycin-producing strain by combined conventional mutagenesis and high-throughput screen method. Wei Sheng Wu Xue Bao 53(7): 758-765, 2013

A high-throughput, near-saturating screen for type III effector genes from Pseudomonas syringae. Proceedings of the National Academy of Sciences of the United States of America 102(7): 2549-2554, 2005

A high-throughput screen for receptor protein tyrosine phosphatase-gamma selective inhibitors. Journal of Biomolecular Screening 16(5): 476-485, 2011

Visualizing microtubule-dependent vasopressin type 2 receptor trafficking using a new high-affinity fluorescent vasopressin ligand. Endocrinology 152(10): 3893-3904, 2011

Development of a high-throughput bioassay to screen melatonin receptor agonists using human melatonin receptor expressing CHO cells. Neuroscience Letters 344(1): 45-48, 2003

Identification of Cosalane as an Inhibitor of Human and Murine CC-Chemokine Receptor 7 Signaling via a High-Throughput Screen. Slas Discovery 23(10): 1083-1091, 2018

A cell-based high-throughput screen for epidermal growth factor receptor pathway inhibitors. Analytical Biochemistry 377(1): 89-94, 2008

Duplex high-throughput flow cytometry screen identifies two novel formylpeptide receptor family probes. Cytometry. Part A 75(3): 253-263, 2008