Novel Protein Kinase Inhibitors Related to Tau Pathology Modulate Tau Protein-Self Interaction Using a Luciferase Complementation Assay
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of the Benzofuropyridines
2.2. Protein Kinase Inhibition
2.3. Tau Protein Interaction Assay
3. Material and Methods
3.1. Chemical Reagents and Instruments
3.2. General Procedure for the Synthesis of Compounds 1
3.3. General Procedure for the Synthesis of Compounds 2
3.4. General Procedure for the Synthesis of Compounds 3 and 4
3.5. General Procedure for the Synthesis of 3-Hydroxy Compounds 3e and 4c
3.6. Protein Kinase Assay
3.7. Tau Protein Phosphorylation Assay
3.8. Tau Protein Interaction Assay
Cell Culture and Transfection
NanoBiT® Luciferase Assay
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
Cpd. | R | Protein Kinase Affinities (µM) a | ||
---|---|---|---|---|
cdk1 | cdk5/p25 | gsk-3β | ||
3a | OEt | 0.17 ± 0.031 | 0.46 ± 0.022 | 0.083 ± 0.034 |
3b | OBn | 2.30 ± 0.33 | n.a. b | 5.80 ± 1.20 |
3c | OMe | 0.14 ± 0.023 | 0.51 ± 0.012 | 0.062 ± 0.023 |
3d | F | 1.40 ± 0.24 | n.a. b | 0.38 ± 0.93 |
3e | OH | 0.013 ± 0.0031 | 0.11 ± 0.043 | 0.024 ± 0.0021 |
4a | OBn | 0.091 ± 0.012 | 2.10 ± 0.24 | 1.60 ± 0.23 |
4b | F | 1.06 ± 0.63 | 160 ± 34 | 190 ± 37 |
4c | OH | 0.77 ± 0.062 | 0.073 ± 0.012 | 0.012 ± 0.013 |
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Holzer, M.; Schade, N.; Opitz, A.; Hilbrich, I.; Stieler, J.; Vogel, T.; Neukel, V.; Oberstadt, M.; Totzke, F.; Schächtele, C.; et al. Novel Protein Kinase Inhibitors Related to Tau Pathology Modulate Tau Protein-Self Interaction Using a Luciferase Complementation Assay. Molecules 2018, 23, 2335. https://doi.org/10.3390/molecules23092335
Holzer M, Schade N, Opitz A, Hilbrich I, Stieler J, Vogel T, Neukel V, Oberstadt M, Totzke F, Schächtele C, et al. Novel Protein Kinase Inhibitors Related to Tau Pathology Modulate Tau Protein-Self Interaction Using a Luciferase Complementation Assay. Molecules. 2018; 23(9):2335. https://doi.org/10.3390/molecules23092335
Chicago/Turabian StyleHolzer, Max, Nico Schade, Ansgar Opitz, Isabel Hilbrich, Jens Stieler, Tim Vogel, Valentina Neukel, Moritz Oberstadt, Frank Totzke, Christoph Schächtele, and et al. 2018. "Novel Protein Kinase Inhibitors Related to Tau Pathology Modulate Tau Protein-Self Interaction Using a Luciferase Complementation Assay" Molecules 23, no. 9: 2335. https://doi.org/10.3390/molecules23092335