Bioaffinity NMR Spectroscopy: Identification of an E-Selectin Antagonist in a Substance Mixture by Transfer NOE

Binding events of ligands to receptors are the key for an understanding of biological processes. Gaining insight into protein-protein and protein-ligand interactions in solution has recently become possible on an atomic level by new NMR spectroscopic techniques. These experiments identify binding events either by looking at the resonance signals of the ligand or the protein. Ideally, both techniques together deliver a complete picture of ligand binding to a receptor. The approaches discussed in this review allow screening of compound libraries as well as a detailed identification of the groups involved in the binding events. Also, characterization of the binding strength and kinetics is possible, competitive binding as well as allosteric effects can be identified, and it has even been possible to identify ligand binding to intact viruses and membrane-bound proteins.

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“…Both effects have been used for the detection of binding activity of ligands. [84][85][86][87][88][89] …”

Section: Transient Transferred Noe Experimentsmentioning

confidence: 99%

NMR Spectroscopy Techniques for Screening and Identifying Ligand Binding to Protein Receptors

2003

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“…Exchange-transferred s NOE measurements were among the first parameters proposed for ligand-based NMR screening [8,71,72]. In NOE-based screens, one monitors intra-ligand NOEs of compound mixtures via 2D-NOESY spectra in the absence and presence of the receptor.…”

Section: Exchange-transferred Noementioning

confidence: 99%

NMR experiments for lead generation in drug discovery

Peng

Moore²,

Abdul-Manan³

2004

Progress in Nuclear Magnetic Resonance Spectroscopy

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“…A strong positive NOE crosspeak is observed for binders, as opposed to weakly negative or zero NOE cross-peaks for the same mixture of compounds in the absence of the target receptor. Thus the sign flip of the NOE cross peak between the free versus bound states acts as a simple binary filter to distinguish binders from non-binders [2,10,56].…”

Section: Iiib 31 Transferred Noe (Trnoe)mentioning

confidence: 99%

Ligand Screening by Saturation-Transfer Difference (STD) NMR Spectroscopy

Krishnan¹

2005

CAC

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NMR based methods to screen for high-affinity ligands have become an indispensable tool for designing rationalized drugs, as these offer a combination of good experimental design of the screening process and data interpretation methods, which together provide unprecedented information on the complex nature of protein-ligand interactions. These methods rely on measuring direct changes in the spectral parameters, that are often simpler than the complex experimental procedures used to study structure and dynamics of proteins. The goal of this review article is to provide the basic details of NMR based ligand-screening methods, with particular focus on the saturation transfer difference (STD) experiment. In addition, we provide an overview of other NMR experimental methods and a practical guide on how to go about designing and implementing them.

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Bioaffinity NMR Spectroscopy: Identification of an E-Selectin Antagonist in a Substance Mixture by Transfer NOE

Cited by 68 publications

References 6 publications

NMR Spectroscopy Techniques for Screening and Identifying Ligand Binding to Protein Receptors

NMR Spectroscopy Techniques for Screening and Identifying Ligand Binding to Protein Receptors

NMR experiments for lead generation in drug discovery

Ligand Screening by Saturation-Transfer Difference (STD) NMR Spectroscopy

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