Affinity screening using competitive binding with fluorine-19 hyperpolarized ligands

Angewandte Chemie
Yaewon Kim, Christian Hilty

Abstract

Fluorine-19 NMR and hyperpolarization form a powerful combination for drug screening. Under a competitive equilibrium with a selected fluorinated reporter ligand, the dissociation constant (K(D)) of other ligands of interest is measurable using a single-scan Carr-Purcell-Meiboom-Gill (CPMG) experiment, without the need for a titration. This method is demonstrated by characterizing the binding of three ligands with different affinities for the serine protease trypsin. Monte Carlo simulations show that the highest accuracy is obtained when about one-half of the bound reporter ligand is displaced in the binding competition. Such conditions can be achieved over a wide range of affinities, allowing for rapid screening of non-fluorinated compounds when a single fluorinated ligand for the binding pocket of interest is known.

References

Apr 1, 1996·Protein Science : a Publication of the Protein Society·I V Kurinov, R W Harrison
Jun 27, 2002·Journal of the American Chemical Society·Claudio DalvitMario Varasi
Sep 26, 2002·Angewandte Chemie·Wolfgang JahnkeDoncho P Uzunov
Feb 14, 2003·Chemistry : a European Journal·Richard E HeathDavid K Smith
Jun 19, 2003·Journal of the American Chemical Society·Claudio DalvitBrian J Stockman
Aug 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jan H Ardenkjaer-LarsenKlaes Golman
Nov 20, 2003·Journal of the American Chemical Society·Claudio DalvitMarina Veronesi
Jul 9, 2004·Drug Discovery Today·Claudio DalvitMarina Veronesi
Sep 22, 2005·Journal of the American Chemical Society·Claudio DalvitRainer Kümmerle
Jun 3, 2008·Angewandte Chemie·Sean Bowen, Christian Hilty
Jan 24, 2009·Journal of Magnetic Resonance·Haukur JóhannessonJan H Ardenkjaer-Larsen
Aug 26, 2009·Journal of the American Chemical Society·Anna VulpettiClaudio Dalvit
May 6, 2010·Physical Chemistry Chemical Physics : PCCP·Sean Bowen, Christian Hilty
May 12, 2010·Physical Chemistry Chemical Physics : PCCP·James LeggettWalter Köckenberger
Dec 7, 2011·Journal of Magnetic Resonance·Michael BatelMatthias Ernst
Oct 2, 2012·Journal of the American Chemical Society·Youngbok LeeChristian Hilty
Sep 10, 2014·ChemMedChem·Roberto BurattoGeoffrey Bodenhausen

Citations

Oct 11, 2016·Analytical Chemistry·Yaewon KimChristian Hilty
Mar 31, 2018·Magnetic Resonance in Chemistry : MRC·Guannan Zhang, Christian Hilty
Jan 16, 2019·Chemical Communications : Chem Comm·Guilherme Vieira de Castro, Alessio Ciulli
Apr 7, 2020·Physical Chemistry Chemical Physics : PCCP·Antonio GennaroWalter Köckenberger
Aug 16, 2016·Magnetic Resonance in Chemistry : MRC·Claudio Dalvit, Martial Piotto
Jul 12, 2020·Journal of Biomolecular NMR·Andras BoeszoermenyiGerhard Wagner

Related Concepts

Benzylamine monosulfate
Benzamidine hydrochloride
Leupeptin, monoacetate, (S)-isomer
Benzamidines
Phenylmethylamine
Fluorine
Leupeptins
Ligands
Monte Carlo Method
In Vivo NMR Spectroscopy

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

The Tendon Seed Network

Tendons are rich in the extracellular matrix and are abundant throughout the body providing essential roles including structure and mobility. The transcriptome of tendons is being compiled to understand the micro-anatomical functioning of tendons. Discover the latest research pertaining to the Tendon Seed Network here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Incretins

Incretins are metabolic hormones that stimulate a decrease in glucose levels in the blood and they have been implicated in glycemic regulation in the remission phase of type 1 diabetes. Here is the latest research.

Chromatin Regulation and Circadian Clocks

The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.

Long COVID-19

“Long Covid-19” describes illness in patients who are reporting long-lasting effects of the SARS-CoV-19 infection, often long after they have recovered from acute Covid-19. Ongoing health issues often reported include low exercise tolerance and breathing difficulties, chronic tiredness, and mental health problems such as post-traumatic stress disorder and depression. This feed follows the latest research into Long Covid.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.