Forbidden Coherence Transfer of 19F Nuclei to Quantitatively Measure the Dynamics of a CF3-Containing Ligand in Receptor-Bound States

Tokunaga, Yuji; Takeuchi, Koh; Shimada, Ichio

doi:10.3390/molecules22091492

Cited by 5 publications

(2 citation statements)

References 48 publications

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“…no conformational entropy loss). It should also be noted that the FCT method is applicable to ligands that are not 13 C labeled 56 as well as ligands containing trifluoromethyl moieties 57 . This example illustrates that FCT experiments that can inform on ps-ns dynamics, in the bound state considering only dipole-induced relaxation, neglecting contributions from CSA (chemical shift anisotropy).…”

Section: Introductionmentioning

confidence: 99%

The role of NMR in leveraging dynamics and entropy in drug design

et al. 2020

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Nuclear magnetic resonance (NMR) spectroscopy has contributed to structure-based drug development (SBDD) in a unique way compared to the other biophysical methods. The potency of a ligand binding to a protein is dictated by the binding free energy, which is an intricate interplay between entropy and enthalpy. In addition to providing the atomic resolution structural information, NMR can help to identify protein-ligand interactions that potentially contribute to the enthalpic component of the free energy. NMR can also illuminate dynamic aspects of the interaction, which correspond to the entropic term of the free energy. The ability of NMR to access both terms in the free energy equation stems from the suite of experiments developed to shed light on various aspects that contribute to both entropy and enthalpy, deepening our understanding of the biological function of macromolecules and assisting to target them in physiological conditions. Here we provide a brief account of the contribution of NMR to SBDD, highlighting hallmark examples and discussing the challenges that demand further method development. In the era of integrated biology, the unique ability of NMR to directly ascertain structural and dynamical aspects of macromolecule and monitor changes in these properties upon engaging a ligand can be combined with computational and other structural and biophysical methods to provide a more complete picture of the energetics of drug engagement with the target. Such efforts can be used to engineer better drugs.

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Section: Introductionmentioning

confidence: 99%

The role of NMR in leveraging dynamics and entropy in drug design

et al. 2020

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“…Thus, the information obtained from Ex-FCT experiments can be used to find suitable sites from the point of view of dynamics to introduce modifications for ligand optimization. It should also be noted that the FCT method is applicable to non-labeled ligands as well as ligands containing trifluoromethyl moieties [112].…”

Section: Utilization Of Dynamics Information For Drug Designmentioning

confidence: 99%

Spotlight on the Ballet of Proteins: The Structural Dynamic Properties of Proteins Illuminated by Solution NMR

Tokunaga

Viennet

Arthanari

et al. 2020

IJMS

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Solution NMR spectroscopy is a unique and powerful technique that has the ability to directly connect the structural dynamics of proteins in physiological conditions to their activity and function. Here, we summarize recent studies in which solution NMR contributed to the discovery of relationships between key dynamic properties of proteins and functional mechanisms in important biological systems. The capacity of NMR to quantify the dynamics of proteins over a range of time scales and to detect lowly populated protein conformations plays a critical role in its power to unveil functional protein dynamics. This analysis of dynamics is not only important for the understanding of biological function, but also in the design of specific ligands for pharmacologically important proteins. Thus, the dynamic view of structure provided by NMR is of importance in both basic and applied biology.

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Feasibility of trifluoromethyl TROSY NMR at high magnetic fields

Klein

Sykes

2019

J Biomol NMR

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Forbidden Coherence Transfer of 19F Nuclei to Quantitatively Measure the Dynamics of a CF3-Containing Ligand in Receptor-Bound States

Cited by 5 publications

References 48 publications

The role of NMR in leveraging dynamics and entropy in drug design

The role of NMR in leveraging dynamics and entropy in drug design

Spotlight on the Ballet of Proteins: The Structural Dynamic Properties of Proteins Illuminated by Solution NMR

Feasibility of trifluoromethyl TROSY NMR at high magnetic fields

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