Spin-Lattice Relaxation Time in Drug Discovery and Design

Figueroa‐Villar, José Daniel; Tinoco, Luzineide W.

doi:10.2174/156802609789207082

Cited by 19 publications

(17 citation statements)

References 97 publications

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“…In the literature, there are very few examples where the 19 F longitudinal relaxation rate has been used to assess the binding (e.g. Figueroa‐Villar and Tinoco and Beringhelli et al …”

Section: Introductionmentioning

confidence: 99%

“…In the literature, there are very few examples where the 19 F longitudinal relaxation rate has been used to assess the binding (e.g. Figueroa-Villar and Tinoco [27] and Beringhelli et al [28] ). Here, we report a theoretical and experimental analysis of the 19 F longitudinal and transverse relaxation rates at different magnetic fields and propose methods for improving the 19 F sensitivity and the dynamic range of 19 F ligand-based NMR screening, particularly when working with low magnetic field NMR spectrometers.…”

Section: Introductionmentioning

confidence: 99%

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¹⁹F NMR transverse and longitudinal relaxation filter experiments for screening: a theoretical and experimental analysis

Dalvit

Piotto

2016

Magnetic Reson in Chemistry

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Ligand-based F NMR screening represents an efficient approach for performing binding assays. The high sensitivity of the methodology to receptor binding allows the detection of weak affinity ligands. The observable NMR parameters that are typically used are the F transverse relaxation rate and isotropic chemical shift. However, there are few cases where the F longitudinal relaxation rate should also be used. A theoretical and experimental analysis of the F NMR transverse and longitudinal relaxation rates at different magnetic fields is presented along with proposed methods for improving the sensitivity and dynamic range of these experiments applied to fragment-based screening. Copyright © 2016 John Wiley & Sons, Ltd.

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“…In the literature, there are very few examples where the 19 F longitudinal relaxation rate has been used to assess the binding (e.g. Figueroa‐Villar and Tinoco and Beringhelli et al …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

¹⁹F NMR transverse and longitudinal relaxation filter experiments for screening: a theoretical and experimental analysis

Dalvit

Piotto

2016

Magnetic Reson in Chemistry

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“…On the other hand, when the ligand-target complex possess mass lower than 70 kD, it is possible to determine their complete structure and its dynamic condition by NMR. 2,3 However, if their mass targets are more than 100 kD, the NMR method is generally not available for their complete ligand-target complex structure determination, but in this case the NMR can be used to determine the interaction of the ligand with the target, especially discovering which areas of the ligand are the most effective for interacting sessions with the target, 4,5 being this the most effective method to study the interaction of pharmacological ligands with any type of targets. In order to determine by NMR which is the target site of interaction with the ligand it is necessary to execute the ligand competition with the previously described inhibitors, which is a process that confirms its interaction with the specific regions of the target, especially with the active sites of the enzymes.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Three-Dimensional Structure, Conformation and Correct Chemical Shift Assignment Determination of Pharmaceutical Molecules by NMR and Molecular Modeling

Azeredo¹,

Sales²,

Figueroa‐Villar³

2016

J. Braz. Chem. Soc.

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This work includes the synthesis of phenanthrenequinone guanylhydrazone and phenanthro [9,10-e][1,2,4]triazin-3-amine to be tested as intercalate with DNA for treatment of cancer. The other synthesized product, 2-[(4-chlorophenylamino)methylene]malononitrile, was designed for future determination of its activity against leishmaniasis. A common problem about some articles on the literature is that some previously published compounds display error of their molecular structures. In this article it is shown the application of several procedures of nuclear magnetic resonance (NMR) to determine the complete molecular structure and the non questionable chemical shift assignment of the synthesized compounds, and also their analysis by molecular modeling to confirm the NMR results. To determine the capacity of pharmacological compounds to interact with biological targets is determined by docking. This work is to motivate the application of NMR and molecular modeling on organic synthesis, being a process that is very important for the study of the prepared compounds as interactions with biological targets by NMR.

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“…In this short report, an investigation was carried out to evaluate whether amide-lipase complexes could be detected by NMR via the monitoring of changes in the STD experiment and relaxation behavior 8 for design the enzymatic kinetic resolution of organic amines by lipases (Scheme 1). The amines compounds have been chosen due to their great importance in biocatalysis 9 and especially in the pharmaceutical industry since a huge number of molecule drug candidates have nitrogen atom.…”

Section: Introductionmentioning

confidence: 99%

Simplification of Lipase Design in the Enzymatic Kinetic Resolution of Amines by Saturation Transfer Difference NMR

Silva¹,

Pietrobom²

2016

Journal of the Brazilian Chemical Society

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In this work, we demonstrate a nuclear magnetic resonance (NMR) method for racemic amide and lipase interaction as a first-pass design method in the enzymatic kinetic resolution of amines. As a novel adaptation of commonly used protein-ligand screening NMR methodologies, this approach relies upon a lipase-amide interaction wherein the time-consuming is reduced drastically and new insights are produced during the development of biocatalysis reactions. Keywords: STD NMR, biocatalysis, enzymatic kinetic resolution, amines IntroductionNowadays, the development of new methods for preparing chiral organic compounds is a major goal of synthetic organic chemists 1 due recognized importance of chirality in biological processes by differences in affinity that each enantiomer presents for receptors and/ or enzymes. 2 Biocatalysis, that consists in the use of enzymes as catalysts, is one of the most efficient routes to enantiopure compounds. 3 The growth of biocatalysis is because of the production and discovery of new enzymes and applications in a wide variety of chemical reactions. 4 The design and optimization of biocatalytic reactions are based on the same rules as traditional organic reactions, such as temperature, pH, substrate and other features. However, the insights about how these parameters affect the performance of enzymatic reaction are a harder task. These difficulties are inserted into any field in which employs biological systems. Furthermore, the evaluation of enzymes that catalyze new organic reactions is a complex activity and time consuming, requiring a tedious labor intensive process that is generally referred as an enantiomeric excess (ee), turnover number (TON), yield (%), time (hours or days) and experimental conditions.The enzymatic reaction requires an interaction of active site of the enzyme to the substrate. In this context, nuclear magnetic resonance (NMR) has become a powerful technique to advance studies of enzyme-substrate (proteinligand) interactions.5 Numerous NMR techniques have been used for characterizing these complexes. One technique that has exhibited promise for rapid screening, the saturation transfer difference (STD), utilizes cross relaxation. 6STD NMR consists of applying a selective radio frequency pulse to a macromolecule at a resonance where no ligand signals are present. The magnetization is transferred to the bound ligands by spin-diffusion. 7 Moreover, STD NMR allows the combination with almost any type of NMR experiment enabling a variety of investigations.In this short report, an investigation was carried out to evaluate whether amide-lipase complexes could be detected by NMR via the monitoring of changes in the STD experiment and relaxation behavior 8 for design the enzymatic kinetic resolution of organic amines by lipases (Scheme 1). The amines compounds have been chosen due to their great importance in biocatalysis 9 and especially in the pharmaceutical industry since a huge number of molecule drug candidates have nitrogen atom. 10 The chiral amines are also used as st...

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Spin-Lattice Relaxation Time in Drug Discovery and Design

Cited by 19 publications

References 97 publications

¹⁹F NMR transverse and longitudinal relaxation filter experiments for screening: a theoretical and experimental analysis

¹⁹F NMR transverse and longitudinal relaxation filter experiments for screening: a theoretical and experimental analysis

Synthesis, Three-Dimensional Structure, Conformation and Correct Chemical Shift Assignment Determination of Pharmaceutical Molecules by NMR and Molecular Modeling

Simplification of Lipase Design in the Enzymatic Kinetic Resolution of Amines by Saturation Transfer Difference NMR

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Spin-Lattice Relaxation Time in Drug Discovery and Design

Cited by 19 publications

References 97 publications

19F NMR transverse and longitudinal relaxation filter experiments for screening: a theoretical and experimental analysis

19F NMR transverse and longitudinal relaxation filter experiments for screening: a theoretical and experimental analysis

Synthesis, Three-Dimensional Structure, Conformation and Correct Chemical Shift Assignment Determination of Pharmaceutical Molecules by NMR and Molecular Modeling

Simplification of Lipase Design in the Enzymatic Kinetic Resolution of Amines by Saturation Transfer Difference NMR

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¹⁹F NMR transverse and longitudinal relaxation filter experiments for screening: a theoretical and experimental analysis

¹⁹F NMR transverse and longitudinal relaxation filter experiments for screening: a theoretical and experimental analysis