Transverse and longitudinal relaxation times (T1? and T1) have been widely exploited in NMR to probe the binding of ligands and putative drugs to target proteins. We have shown recently that long-lived states (LLS) can be more sensitive to ligand binding. LLS can be excited if the ligand comprises at least two coupled spins. Herein we broaden the scope of ligand screening by LLS to arbitrary ligands by covalent attachment of a functional group, which comprises a pair of coupled protons that are isolated from neighboring magnetic nuclei. The resulting functionalized ligands have longitudinal relaxation times T1(1H) that are sufficiently long to allow the powerful combination of LLS with dissolution dynamic nuclear polarization (D-DNP). Hyperpolarized weak “spy ligands” can be displaced by high-affinity competitors. Hyperpolarized LLS allow one to decrease both protein and ligand concentrations to micromolar levels and to significantly increase sample throughput.
Long-Lived States of Magnetically Equivalent Spins Populated by Dissolution-DNP and Revealed by Enzymatic Reactions
From The DNP-NMR Blog:
Long-Lived States of Magnetically Equivalent Spins Populated by Dissolution-DNP and Revealed by Enzymatic Reactions
Bornet, A., et al., Long-Lived States of Magnetically Equivalent Spins Populated by Dissolution-DNP and Revealed by Enzymatic Reactions. Chemistry, 2014. 20(51): p. 17113-8.
http://www.ncbi.nlm.nih.gov/pubmed/25346515
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12-17-2014 09:43 PM
Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR
From The DNP-NMR Blog:
Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR
Buratto, R., et al., Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR. ChemMedChem, 2014: p. n/a-n/a.
http://www.ncbi.nlm.nih.gov/pubmed/25196781
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09-27-2014 01:54 AM
[NMR paper] Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR.
Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR.
Related Articles Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR.
ChemMedChem. 2014 Sep 4;
Authors: Buratto R, Bornet A, Milani J, Mammoli D, Vuichoud B, Salvi N, Singh M, Laguerre A, Passemard S, Gerber-Lemaire S, Jannin S, Bodenhausen G
Abstract
Transverse and longitudinal relaxation times (T1? and T1 ) have been widely exploited in NMR to probe the binding of ligands and putative drugs to target proteins. We have shown recently that long-lived...
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09-10-2014 11:24 AM
[NMR paper] Exploring Weak Ligand-Protein Interactions by Long-Lived NMR States : Improved Contrast in Fragment-Based Drug Screening.
Exploring Weak Ligand-Protein Interactions by Long-Lived NMR States : Improved Contrast in Fragment-Based Drug Screening.
Related Articles Exploring Weak Ligand-Protein Interactions by Long-Lived NMR States : Improved Contrast in Fragment-Based Drug Screening.
Angew Chem Int Ed Engl. 2014 Sep 4;
Authors: Buratto R, Mammoli D, Chiarparin E, Williams G, Bodenhausen G
Abstract
Ligands that have an affinity for protein targets can be screened very effectively by exploiting favorable properties of long-lived states (LLS) in NMR...
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09-10-2014 11:24 AM
Long-lived nuclear spin states in methyl groups and quantum-rotor-induced polarization
From The DNP-NMR Blog:
Long-lived nuclear spin states in methyl groups and quantum-rotor-induced polarization
Meier, B., et al., Long-lived nuclear spin states in methyl groups and quantum-rotor-induced polarization. J Am Chem Soc, 2013. 135(50): p. 18746-9.
http://www.ncbi.nlm.nih.gov/pubmed/24252212
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02-13-2014 01:42 AM
Boosting the Sensitivityof Ligand–ProteinScreening by NMR of Long-Lived States
Boosting the Sensitivityof Ligand–ProteinScreening by NMR of Long-Lived States
Nicola Salvi, Roberto Buratto, Aure?lien Bornet, Simone Ulzega, Inmaculada Rentero Rebollo, Alessandro Angelini, Christian Heinis and Geoffrey Bodenhausen
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja303301w/aop/images/medium/ja-2012-03301w_0004.gif
Journal of the American Chemical Society
DOI: 10.1021/ja303301w
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/jacsat/~4/xsuzyMhXJF4
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06-28-2012 07:54 AM
Long-Lived States to Monitor Protein Unfolding by Proton NMR.
Long-Lived States to Monitor Protein Unfolding by Proton NMR.
Long-Lived States to Monitor Protein Unfolding by Proton NMR.
Chemphyschem. 2011 Aug 31;
Authors: Bornet A, Ahuja P, Sarkar R, Fernandes L, Hadji S, Lee SY, Haririnia A, Fushman D, Bodenhausen G, Vasos PR
Abstract
The relaxation of long-lived states (LLS) corresponds to the slow return to statistical thermal equilibrium between symmetric and antisymmetric proton spin states. This process is remarkably sensitive to the presence of external spins and can be used to obtain...
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09-02-2011 05:40 PM
[NMR paper] A high-resolution NMR study of long-lived water molecules in both oxidation states of
A high-resolution NMR study of long-lived water molecules in both oxidation states of a minimal cytochrome c.
Related Articles A high-resolution NMR study of long-lived water molecules in both oxidation states of a minimal cytochrome c.
Biochemistry. 2003 Apr 1;42(12):3457-63
Authors: Bertini I, Ghosh K, Rosato A, Vasos PR
The interaction of water with oxidized and reduced cytochrome c from the Gram-positive bacterium Bacillus pasteurii (a 71-amino acid long monoheme cytochrome) is investigated through CLEANEX experiments and (15)N-edited...
Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR
Linear Mode
