Related ArticlesNMR-Based Strategies to Elucidate Bioactive Conformations of Weakly Binding Ligands.
Top Curr Chem. 2008;273:1-14
Authors: Blommers MJ, Strauss A, Geiser M, Ramage P, Sparrer H, Jahnke W
Abstract
Key processes in molecular biology are regulated by interactions between biomolecules. Protein-proteinand protein-ligand interactions, e.g., in signal transduction pathways, rely on the subtle interactionsbetween atoms at the binding interface of the involved molecules. Because biomolecules often havemany interacting partners, these interactions are not necessarily strong. The study of molecularrecognition gives insight into the complex network of signaling in life and is the basis of structure-baseddrug design.In the situation where the interaction is weak, one of the traditional methods that can be appliedto obtain structural information (internuclear distances) of the bound ligand is the so-called transferredNOE (trNOE) method. Recently, it became possible to use transferred cross-correlated relaxation (trCCR)to directly measure dihedral angles. The combined use of these two techniques significantly improvesthe precision of the structure determination of ligands weakly bound to macromolecules.The application of these techniques will be discussed in detail for a*peptide derived fromIKK? bound to the protein NEMO that plays an important rolein the NF?B pathway.
Lysine methylation strategies for characterizing protein conformations by NMR
Lysine methylation strategies for characterizing protein conformations by NMR
Abstract In the presence of formaldehyde and a mild reducing agent, reductive methylation is known to achieve near complete dimethylation of protein amino groups under non-denaturing conditions, in aqueous media. Amino methylation of proteins is employed in mass spectrometric, crystallographic, and NMR studies. Where biosynthetic labeling is prohibitive, amino 13C-methylation provides an attractive option for monitoring folding, kinetics, proteinâ??protein and protein-DNA interactions by NMR. Here, we...
[NMR paper] Strategies for the NMR-based identification and optimization of allosteric protein kinase inhibitors.
Strategies for the NMR-based identification and optimization of allosteric protein kinase inhibitors.
Related Articles Strategies for the NMR-based identification and optimization of allosteric protein kinase inhibitors.
Chembiochem. 2005 Sep;6(9):1607-10
Authors: Jahnke W, Blommers MJ, Fernández C, Zwingelstein C, Amstutz R
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[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.
Related Articles Competition STD NMR for the detection of high-affinity ligands and NMR-based screening.
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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[NMR paper] NMR-based methods and strategies for drug discovery.
NMR-based methods and strategies for drug discovery.
Related Articles NMR-based methods and strategies for drug discovery.
Chem Soc Rev. 2003 Nov;32(6):365-72
Authors: Salvatella X, Giralt E
Nuclear Magnetic Resonance (NMR) spectroscopy has long been a favourite tool of chemists interested in host-guest systems because it permits access to a wealth of information about the molecular recognition reaction. NMR has evolved dramatically in the last 15 years and, in parallel with the development of NMR methods for the determination of protein...
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[NMR paper] MS/NMR: a structure-based approach for discovering protein ligands and for drug desig
MS/NMR: a structure-based approach for discovering protein ligands and for drug design by coupling size exclusion chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy.
Related Articles MS/NMR: a structure-based approach for discovering protein ligands and for drug design by coupling size exclusion chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy.
Anal Chem. 2001 Feb 1;73(3):571-81
Authors: Moy FJ, Haraki K, Mobilio D, Walker G, Powers R, Tabei K, Tong H, Siegel MM
A protocol is described...
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[NMR paper] Binding of sugar ligands to Ca(2+)-dependent animal lectins. I. Analysis of mannose b
Binding of sugar ligands to Ca(2+)-dependent animal lectins. I. Analysis of mannose binding by site-directed mutagenesis and NMR.
Related Articles Binding of sugar ligands to Ca(2+)-dependent animal lectins. I. Analysis of mannose binding by site-directed mutagenesis and NMR.
J Biol Chem. 1994 Jun 3;269(22):15505-11
Authors: Iobst ST, Wormald MR, Weis WI, Dwek RA, Drickamer K
The Ca(2+)-dependent carbohydrate-recognition domain (CRD) of rat serum mannose-binding protein has been subjected to site-directed mutagenesis to determine the...
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Precise structural determination of weakly binding peptides by utilizing dihedral ang
Abstract Structural determination of target-bound conformations of peptides is of primary importance for the optimization of peptide ligands and peptideâ??mimetic design. In the structural determination of weakly binding ligands, transferred nuclear Overhauser effect (TrNOE) methods have been widely used. However, not many distance constraints can be obtained from small peptide ligands by TrNOE, especially for peptides bound to a target molecule in an extended conformation. Therefore, for precise structural determination of weakly binding peptides, additional structural constraints are...
NMR-Based Strategies to Elucidate Bioactive Conformations of Weakly Binding Ligands.
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