Related ArticlesPI by NMR: Probing CH-? Interactions in Protein-Ligand Complexes by NMR.
Angew Chem Int Ed Engl. 2020 May 18;:
Authors: Platzer G, Mayer M, Beier A, Brüschweiler S, Fuchs JE, Engelhardt H, Geist L, Bader G, Schörghuber J, Lichtenecker R, Wolkersdorfer B, Kessler D, McConnell DB, Konrat R
Abstract
While CH-?-interactions with target proteins are crucial determinants for the affinity of arguably every drug molecule, no method exists to directly measure the strength of individual CH-? interactions in drug-protein complexes. Here we present a fast and reliable methodology called PI (? interactions) by NMR, which can differentiate the strength of protein-ligand CH-? interactions in solution. By combining selective amino-acid side-chain labeling with 1 H- 13 C NMR, we are able to identify specific protein protons of side-chains engaged in CH-? interactions with aromatic ring-systems of a ligand, based solely on 1 H chemical shift values of the interacting protein aromatic ring protons. The information encoded in the chemical shifts induced by such interactions serves as a proxy for the strength of each individual CH-? interaction. PI by NMR changes the paradigm by which chemists can optimize the potency of drug candidates: direct determination of individual ?-interactions rather than averaged measures of all interactions.
PMID: 32421895 [PubMed - as supplied by publisher]
[NMR paper] Trimethylsilyl tag for probing protein-ligand interactions by NMR.
Trimethylsilyl tag for probing protein-ligand interactions by NMR.
Trimethylsilyl tag for probing protein-ligand interactions by NMR.
J Biomol NMR. 2018 Mar 21;:
Authors: Becker W, Adams LA, Graham B, Wagner GE, Zangger K, Otting G, Nitsche C
Abstract
Protein-ligand titrations can readily be monitored with a trimethylsilyl (TMS) tag. Owing to the intensity, narrow line shape and unique chemical shift of a TMS group, dissociation constants can be determined from straightforward 1D 1H-NMR spectra not only in the fast but also in...
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Trimethylsilyl tag for probing proteinâ??ligand interactions by NMR
Trimethylsilyl tag for probing proteinâ??ligand interactions by NMR
Abstract
Proteinâ??ligand titrations can readily be monitored with a trimethylsilyl (TMS) tag. Owing to the intensity, narrow line shape and unique chemical shift of a TMS group, dissociation constants can be determined from straightforward 1D 1H-NMR spectra not only in the fast but also in the slow exchange limit. The tag is easily attached to cysteine residues and a sensitive reporter of ligand binding also at sites where it does not interfere with ligand binding or catalytic...
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[NMR paper] Overview of Probing Protein-Ligand Interactions Using NMR.
Overview of Probing Protein-Ligand Interactions Using NMR.
Overview of Probing Protein-Ligand Interactions Using NMR.
Curr Protoc Protein Sci. 2015;81:17.18.1-17.18.24
Authors: Aguirre C, Cala O, Krimm I
Abstract
Nuclear magnetic resonance (NMR) is a powerful technique for the study and characterization of protein-ligand interactions. In this unit we review both experiments where the NMR spectrum of the protein is observed (protein-observed NMR experiments) and those where the NMR spectra of the ligand is observed...
[NMR paper] Probing the binding entropy of ligand-protein interactions by NMR.
Probing the binding entropy of ligand-protein interactions by NMR.
Related Articles Probing the binding entropy of ligand-protein interactions by NMR.
Chembiochem. 2005 Sep;6(9):1585-91
Authors: Homans SW
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[NMR paper] Probing site-specific interactions in protein-DNA complexes using heteronuclear NMR s
Probing site-specific interactions in protein-DNA complexes using heteronuclear NMR spectroscopy and molecular modeling: binding of Cro repressor to OR3.
Related Articles Probing site-specific interactions in protein-DNA complexes using heteronuclear NMR spectroscopy and molecular modeling: binding of Cro repressor to OR3.
J Biomol Struct Dyn. 1998 Aug;16(1):13-20
Authors: Edwards CA, Tung CS, Silks LA, Gatewood JM, Fee JA, Mariappan SV
In this paper, a general method is developed to study site-specific interactions in DNA-protein complexes...
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[NMR paper] On the ligand-protein and ligand-flavin interactions in NADPH-adrenodoxin reductase a
On the ligand-protein and ligand-flavin interactions in NADPH-adrenodoxin reductase as studied by 31P- and 13C-NMR. Use of 13C-enriched FAD as a probe.
Related Articles On the ligand-protein and ligand-flavin interactions in NADPH-adrenodoxin reductase as studied by 31P- and 13C-NMR. Use of 13C-enriched FAD as a probe.
J Biochem. 1991 Jan;109(1):144-9
Authors: Fujii S, Nonaka Y, Okamoto M, Miura R
The interaction between 2',5'-ADP and NADPH-adrenodoxin reductase from bovine adrenocortical mitochondria was examined by titrating the enzyme with...
PI by NMR: Probing CH-? Interactions in Protein-Ligand Complexes by NMR.
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