Related ArticlesNMR-based drug development and improvement against malignant melanoma - implications for the MIA protein family.
Curr Med Chem. 2017 Jun 08;:
Authors: Arnolds O, Zhong X, Yip KT, Schöpel M, Kohl B, Pütz S, Abdel-Jalil R, Stoll R
Abstract
The Melanoma Inhibitory Activity (MIA) protein is strongly expressed and secreted by malignant melanoma cells and was shown to promote melanoma development and invasion. The MIA protein was the first extracellular protein shown to adopt a Src homology 3 (SH3) domain-like fold in solution that can bind to fibronectin type III domains. Together with MIA, the homologous proteins OTOR (or FDP), MIA-2, and TANGO (or MIA-3) constitute a protein family of non-cytoplasmic and - except for full-length TANGO and TANGO1-like (TALI) - extracellular SH3-domain containing proteins. Members of this protein family modulate collagen maturation and export, cartilage development, cell attachment in the extracellular matrix, and melanoma metastasis. These proteins may thus serve as promising targets for drug development against malignant melanoma. For the last twenty years, NMR spectroscopy has become a powerful technique in medicinal chemistry. While traditional high throughput screenings only report on the activity or affinity of low molecular weight compounds, NMR spectroscopy does not only relate the structure of those compounds with their activity, but it can also unravel structural information on the ligand binding site on the protein at atomic resolution. Based on the molecular details of the interaction between the ligand and its target protein, the binding affinities of initial fragment hits can be further improved more efficiently in order to generate lead structures that exhibit significant therapeutic effects. The NMR-based approach promises to greatly contribute to the quest for low molecular weight compounds that ultimately could yield drugs to treat skin-related diseases such as malignant melanoma more effectively.
PMID: 28595551 [PubMed - as supplied by publisher]
[NMR paper] Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations.
Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations.
Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations.
Proc Natl Acad Sci U S A. 2014 Oct 13;
Authors: Baxa MC, Haddadian EJ, Jumper JM, Freed KF, Sosnick TR
Abstract
The loss of conformational entropy is a major contribution in the thermodynamics of protein folding. However, accurate determination of the quantity...
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[NMR paper] Structure-based drug design: NMR-based approach for ligand-protein interactions.
Structure-based drug design: NMR-based approach for ligand-protein interactions.
Related Articles Structure-based drug design: NMR-based approach for ligand-protein interactions.
Drug Discov Today Technol. 2006;3(3):241-5
Authors: Zhang X, Tang H, Ye C, Liu M
Abstract
The realization of the powerfulness in analyzing ligand-protein interactions at the atomic resolution has made NMR techniques increasingly attractive in drug discovery and development. With some significant new method developments during the past few years,...
New Protein Evolution Insight Could Improve Drug Design - Drug Discovery & Development
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New Protein Evolution Insight Could Improve Drug Design
Drug Discovery & Development
The team used a variety of techniques to characterize the two versions of the enzyme, including X-ray crystallography and nuclear magnetic resonance, analyses of DHFR amino-acid sequences and evaluations of the enzyme's functionality in cells and in ...
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New Protein Evolution Insight Could Improve Drug Design - Drug Discovery & Development
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Researchers Look at Averting Drug Resistance - Drug Discovery & Development
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Researchers Look at Averting Drug Resistance
Drug Discovery & Development
Kern and her team studied the protein using nuclear magnetic resonance spectroscopy, adding a drug mimetic in order to learn how the structure EmrE was designed and how it functioned as it was transportingâ??moving the drug from the inside of the cell ...
Researchers Look at Averting Drug Resistance - Drug Discovery & Development
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[NMR paper] Sensitivity improvement in 19F NMR-based screening experiments: theoretical considerations and experimental applications.
Sensitivity improvement in 19F NMR-based screening experiments: theoretical considerations and experimental applications.
Related Articles Sensitivity improvement in 19F NMR-based screening experiments: theoretical considerations and experimental applications.
J Am Chem Soc. 2005 Sep 28;127(38):13380-5
Authors: Dalvit C, Mongelli N, Papeo G, Giordano P, Veronesi M, Moskau D, Kümmerle R
NMR-based binding and functional screening performed with FAXS (fluorine chemical shift anisotropy and exchange for screening) and 3-FABS (three fluorine atoms...
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Fluorine-Protein Interactions and (19)F NMR Isotropic Chemical Shifts: An Empirical Correlation with Implications for Drug Design.
Fluorine-Protein Interactions and (19)F NMR Isotropic Chemical Shifts: An Empirical Correlation with Implications for Drug Design.
Related Articles Fluorine-Protein Interactions and (19)F NMR Isotropic Chemical Shifts: An Empirical Correlation with Implications for Drug Design.
ChemMedChem. 2010 Nov 29;
Authors: Dalvit C, Vulpetti A
An empirical correlation between the fluorine isotropic chemical shifts, measured by (19)F NMR spectroscopy, and the type of fluorine-protein interactions observed in crystal structures is presented. The CF, CF(2), and...
NMR-based drug development and improvement against malignant melanoma - implications for the MIA protein family.
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