Kim, Y. and C. Hilty, Affinity screening using competitive binding with fluorine-19 hyperpolarized ligands. Angew Chem Int Ed Engl, 2015. 54(16): p. 4941-4.
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.
Polarization Transfer from Ligands Hyperpolarized by Dissolution Dynamic Nuclear Polarization for Screening in Drug Discovery
From The DNP-NMR Blog:
Polarization Transfer from Ligands Hyperpolarized by Dissolution Dynamic Nuclear Polarization for Screening in Drug Discovery
Min, H., G. Sekar, and C. Hilty, Polarization Transfer from Ligands Hyperpolarized by Dissolution Dynamic Nuclear Polarization for Screening in Drug Discovery. ChemMedChem, 2015. 10(9): p. 1559-63.
http://www.ncbi.nlm.nih.gov/pubmed/26315550
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10-05-2015 07:08 PM
[NMR paper] Ranking high affinity ligands of low solubility by NMR spectroscopy.
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ACS Med Chem Lett. 2011 Jun 9;2(6):485-7
Authors: Landrieu I, Hanoulle X, Fritzinger B, Horvath D, Wieruszeski JM, Lippens G
Abstract
Cyclosporine A (CsA) and its chemical analogues EthVal4Cs, MeVal4Cs, and Me(d-Ala)3EthVal4Cs (Alisporivir) all interact with cyclophilin A (CypA). The latter Alisporivir is a nonimmunosuppressive CsA derivative that has potent anti-HCV properties...
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06-07-2014 07:12 PM
[NMR paper] NMR screening of new carbocyanine dyes as ligands for affinity chromatography.
NMR screening of new carbocyanine dyes as ligands for affinity chromatography.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-2250-98-WileyOnlineLibrary-Button_120x27px_FullText.gif Related Articles NMR screening of new carbocyanine dyes as ligands for affinity chromatography.
J Mol Recognit. 2014 Apr;27(4):197-204
Authors: Cruz C, Boto RE, Drzazga AK, Almeida P, Queiroz JA
Abstract
Four new carbocyanines containing symmetric and asymmetric heterocyclic moieties and N-carboxyalkyl groups have...
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03-05-2014 11:57 PM
[NMR paper] Fluorine NMR-Based Screening on Cell Membrane Extracts.
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ChemMedChem. 2013 Dec 11;
Authors: Veronesi M, Romeo E, Lambruschini C, Piomelli D, Bandiera T, Scarpelli R, Garau G, Dalvit C
Abstract
The possibility of measuring the action of inhibitors of specific enzymatic reactions in intact cells, cell lysates or membrane preparations represents a major advance in the lead discovery process. Despite the relevance of assaying in physiological conditions, only a small...
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12-18-2013 04:00 PM
[NMR paper] Epitope mapping and competitive binding of HSA drug site II ligands by NMR diffusion
Epitope mapping and competitive binding of HSA drug site II ligands by NMR diffusion measurements.
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J Am Chem Soc. 2004 Nov 3;126(43):14258-66
Authors: Lucas LH, Price KE, Larive CK
It is important to characterize drug-albumin binding during drug discovery and lead optimization as strong binding may reduce bioavailability and/or increase the drug's in vivo half-life. Despite knowing about the location of human serum albumin (HSA)...
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11-24-2010 10:03 PM
[NMR paper] Competition STD NMR for the detection of high-affinity ligands and NMR-based screenin
Competition STD NMR for the detection of high-affinity ligands and NMR-based screening.
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Magn Reson Chem. 2004 Jun;42(6):485-9
Authors: Wang YS, Liu D, Wyss DF
The reported competition STD NMR method combines saturation transfer difference (STD) NMR with competition binding experiments to allow the detection of high-affinity ligands that undergo slow chemical exchange on the NMR time-scale. With this technique, the presence of a competing...
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11-24-2010 09:51 PM
[NMR paper] Analysis of competitive binding of ligands to human serum albumin using NMR relaxatio
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J Pharm Biomed Anal. 2004 Feb 4;34(2):247-54
Authors: Cui YF, Bai GY, Li CG, Ye CH, Liu ML
The competitive binding of two ligands, ibuprofen (IBP) and salicylic acid (SAL), to human serum albumin (HSA) was studied by using nuclear magnetic resonance (NMR) relaxation measurements. When the concentration of one ligand was...
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11-24-2010 09:25 PM
[NMR paper] Discovering high-affinity ligands for proteins: SAR by NMR.
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Science. 1996 Nov 29;274(5292):1531-4
Authors: Shuker SB, Hajduk PJ, Meadows RP, Fesik SW
A nuclear magnetic resonance (NMR)-based method is described in which small organic molecules that bind to proximal subsites of a protein are identified, optimized, and linked together to produce high-affinity ligands. The approach is called "SAR by NMR" because structure-activity relationships (SAR) are obtained from...
Affinity screening using competitive binding with fluorine-19 hyperpolarized ligands
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