Evidence map›Paper›PMID 25481736›Full record

ArticleAnalytical biochemistry2015

Isothermal chemical denaturation to determine binding affinity of small molecules to G-protein coupled receptors.

Patrick Ross, Wilhelm Weihofen, Fai Siu, Amy Xie, Hetal Katakia, S Kirk Wright, Ian Hunt, Richard K Brown, Ernesto Freire

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Analytical biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 36% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Fluorescence-Based Protein Stability Monitoring-A Review.International journal of molecular sciences · 2024
    Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Patrick RossAVIA Biosystems, Norton, MA 02766, USA.
Wilhelm WeihofenNovartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Fai SiuNovartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Amy XieNovartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Hetal KatakiaNovartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
S Kirk WrightNovartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Ian HuntNovartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Richard K BrownAVIA Biosystems, Norton, MA 02766, USA.
Ernesto FreireAVIA Biosystems, Norton, MA 02766, USA; Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: ef@jhu.edu.
Novartis (United States) · USAdarza BioSystems (United States) · US

Funding

Understanding Envelope Function in HIV-1 Infection: The Design, Synthesis and Validation of Small Molecule HIV-1 Env InhibitorsP01GM056550 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI ABRAMS, CAMERON F · 1997 to 2018
$31.2M
An Instrument to Determine Protein Stability for Biologics Formulations TestingR44GM096751 · NIGMS · AVIA BIOSYSTEMS, LLC · PI BROWN, RICHARD KENNETH · 2012 to 2013
$1.3M
Development of an Instrument to Determine Protein Stability at any Desired TemperR43GM096751 · NIGMS · AVIA BIOSYSTEMS, LLC · PI BROWN, RICHARD KENNETH · 2011 to 2011
$135k
NIGMS NIH HHS GM056550NIGMS NIH HHS GM096751NIGMS NIH HHS P01 GM056550NIGMS NIH HHS R43 GM096751NIGMS NIH HHS R44 GM096751
6 · The paper itself

Abstract

The determination of accurate binding affinities is critical in drug discovery and development. Several techniques are available for characterizing the binding of small molecules to soluble proteins. The situation is different for integral membrane proteins. Isothermal chemical denaturation has been shown to be a valuable biophysical method to determine, in a direct and label-free fashion, the binding of ligands to soluble proteins. In this study, the application of isothermal chemical denaturation was applied to an integral membrane protein, the A2a G-protein coupled receptor. Binding affinities for a set of 19 small molecule agonists/antagonists of the A2a receptor were determined and found to be in agreement with data from surface plasmon resonance and radioligand binding assays previously reported in the literature. Therefore, isothermal chemical denaturation expands the available toolkit of biophysical techniques to characterize and study ligand binding to integral membrane proteins, specifically G-protein coupled receptors in vitro.

Indexed as

TemperatureAdenosine A2 Receptor AgonistsAdenosine A2 Receptor AntagonistsBiophysicsGuanidineLigandsProtein BindingProtein DenaturationReceptor, Adenosine A2AAdenosine A2 Receptor AgonistsAdenosine A2 Receptor AntagonistsGuanidineLigandsReceptor, Adenosine A2ABinding affinity determinationBinding thermodynamicsChemical denaturationGPCR

Identifiers

PMID25481736
PMCPMC4355058
OpenAlexW2054461066

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.