Co-Aggregation of S100A9 with DOPA and Cyclen-Based Compounds Manifested in Amyloid Fibril Thickening without Altering Rates of Self-Assembly
Abstract
:1. Introduction
2. Results
2.1. Computation Analysis of the Physico-Chemical Properties of Molecular Compounds and Their Prospective Drug Likeness
2.2. Kinetic Analysis of S100A9 Amyloid Formation in the Absence and Presence of DOPA and Cyclen-Based Compounds Monitored by ThT Fluorescence
2.3. AFM Imaging of S100A9 Amyloids Aggregated Alone and Together with Corresponding Compounds
2.4. Titration of S100A9 with DOPA and Cyclen-Based Compounds Followed by Intrinsic Fluorescence
2.5. Ligand Docking
2.6. MD Simulation
3. Discussion
4. Materials and Methods
4.1. Amyloid Fibril Formation
4.2. ThT Fluorescence Assay
4.3. Kinetic Curve Fitting
4.4. AFM Imaging
4.5. Titration of S100A9 with DOPA and Cyclen-Based Compounds Monitored by Intrinsic Fluorescence
4.6. Ligand Docking Studies
4.7. All-Atom MD Studies
4.8. DOPA and Cyclen Ligand Synthesis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AFM | Atomic force microscopy |
Aβ | Amyloid β |
Cyclen | 1,4,7,10-tetraazacyclododecane |
DOPA | L-3,4-dihydroxyphenylalanine |
MD | Molecular dynamic |
ThT | Thioflavin T |
RMSD | Root mean square deviation |
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Protein and Compounds | Kinetic Rate Constants and Their Rations | |||
---|---|---|---|---|
1:1 | 1:10 | |||
k, μM−1s−1 | k/kS100A9 | k, μM−1s−1 | k/kS100A9 | |
S100A9 | 0.066 | 1 | 0.066 | 1 |
DOPA-D-H-DOPA | 0.06 | 0.91 | 0.066 | 1 |
DOPA-H-H-DOPA | 0.077 | 1.17 | 0.134 | 2.03 |
DOPA-D-H | 0.063 | 0.95 | 0.045 | 0.69 |
H-E-cyclen | 0.069 | 1.05 | 0.048 | 0.72 |
DOPA-cyclen | 0.062 | 0.93 | 0.133 | 2.02 |
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Arabuli, L.; Iashchishyn, I.A.; Romanova, N.V.; Musteikyte, G.; Smirnovas, V.; Chaudhary, H.; Svedružić, Ž.M.; Morozova-Roche, L.A. Co-Aggregation of S100A9 with DOPA and Cyclen-Based Compounds Manifested in Amyloid Fibril Thickening without Altering Rates of Self-Assembly. Int. J. Mol. Sci. 2021, 22, 8556. https://doi.org/10.3390/ijms22168556
Arabuli L, Iashchishyn IA, Romanova NV, Musteikyte G, Smirnovas V, Chaudhary H, Svedružić ŽM, Morozova-Roche LA. Co-Aggregation of S100A9 with DOPA and Cyclen-Based Compounds Manifested in Amyloid Fibril Thickening without Altering Rates of Self-Assembly. International Journal of Molecular Sciences. 2021; 22(16):8556. https://doi.org/10.3390/ijms22168556
Chicago/Turabian StyleArabuli, Lili, Igor A. Iashchishyn, Nina V. Romanova, Greta Musteikyte, Vytautas Smirnovas, Himanshu Chaudhary, Željko M. Svedružić, and Ludmilla A. Morozova-Roche. 2021. "Co-Aggregation of S100A9 with DOPA and Cyclen-Based Compounds Manifested in Amyloid Fibril Thickening without Altering Rates of Self-Assembly" International Journal of Molecular Sciences 22, no. 16: 8556. https://doi.org/10.3390/ijms22168556
APA StyleArabuli, L., Iashchishyn, I. A., Romanova, N. V., Musteikyte, G., Smirnovas, V., Chaudhary, H., Svedružić, Ž. M., & Morozova-Roche, L. A. (2021). Co-Aggregation of S100A9 with DOPA and Cyclen-Based Compounds Manifested in Amyloid Fibril Thickening without Altering Rates of Self-Assembly. International Journal of Molecular Sciences, 22(16), 8556. https://doi.org/10.3390/ijms22168556