Ligand-Based Discovery of a Small Molecule as Inhibitor of α-Synuclein Amyloid Formation
Abstract
:1. Introduction
2. Results and Discussion
2.1. Similarity-Based Virtual Screening (VS)
2.2. Thioflavin-T Fluorescence Test
2.3. Computational Studies to Predict the Binding Site
3. Materials and Methods
3.1. Ligand-Based Virtual Screening
3.2. In Vitro Testing (Th-T Fluorescence, Light Scattering, and Electron Microscopy Assays)
3.3. Analysis of Potential Binding Sites
3.4. Molecular Docking Studies
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Query Cmpds | FP2 | Electroshape a | Spectrophores b |
---|---|---|---|
SC-D | 3 (3) | 33 (33) | 400 (108) |
ZPD-2 | 2 (2) | 400 (178) | 400 (39) |
Putative Binding Sites | Residues |
---|---|
SITE A | VAL52A; ALA53A; THR54A; VAL55A; ALA56A; GLU57A; LYS58A; THR59A; LYS60A; GLU61A; VAL70A; VAL71A; THR72A; GLY73A; VAL74A; THR75A; THR92A; GLY51B; VAL52B; ALA53B; THR54B; VAL55B; ALA56B; GLU57B; LYS58B; THR59B; LYS60B; GLU61B; GLN62B; THR64B; VAL66B; VAL70B; VAL71B; THR72B; GLY73B; VAL74B; THR75B; ALA76B; THR92B; HIS50C; GLY51C; VAL52C; ALA53C; THR54C; VAL55C; ALA56C; GLU57C; LYS58C; THR59C; LYS60C; GLU61C; GLN62C; THR54C; VAL66C; ALA69C; VAL70C; VAL71C; THR72C; GLY73C; VAL74C; THR75C; ALA76C; THR92C; GLY93C; GLY51D; VAL52D; ALA53D; THR54D; VAL55D; ALA56D; GLU57D; LYS58D; THR59D; LYS60D; GLU61D; GLN62D; THR64D; VAL70D; VAL71D; THR72D; GLY73D; VAL74D; THR75D; ALA76D; THR92D; GLY51E; VAL52E; ALA53E; THR54E; VAL55E; ALA56E; GLU57E; LYS58E; THR59E; LYS60E; GLU61E; VAL70E; VAL71E; THR72E; GLY73E; VAL74E; THR75E |
SITE B | VAL40A; GLY41A; SER42A; LYS43A; THR44A; LYS45A; GLU46A; VAL48A; TYR39B; VAL40B; GLY41B; SER42B; LYS43B; THR44B; LYS45B; GLU46B; GLY47B; VAL48B; VAL49B; HIS50B; TYR39C; VAL40C; GLY41C; SER42C; LYS43C; THR44C; LYS45C; GLU46C; GLY47C; VAL48C; VAL49C; HIS50C; TYR39D; VAL40D; GLY41D; SER42D; LYS43D; THR44D; LYS45D; GLU46D; GLY47D; VAL48D; VAL49D; HIS50D; GLY41E; SER42E; LYS43E; THR44E; LYS45E; GLU46E; VAL48E; VAL49E; HIS50E. |
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De Luca, L.; Vittorio, S.; Peña-Díaz, S.; Pitasi, G.; Fornt-Suñé, M.; Bucolo, F.; Ventura, S.; Gitto, R. Ligand-Based Discovery of a Small Molecule as Inhibitor of α-Synuclein Amyloid Formation. Int. J. Mol. Sci. 2022, 23, 14844. https://doi.org/10.3390/ijms232314844
De Luca L, Vittorio S, Peña-Díaz S, Pitasi G, Fornt-Suñé M, Bucolo F, Ventura S, Gitto R. Ligand-Based Discovery of a Small Molecule as Inhibitor of α-Synuclein Amyloid Formation. International Journal of Molecular Sciences. 2022; 23(23):14844. https://doi.org/10.3390/ijms232314844
Chicago/Turabian StyleDe Luca, Laura, Serena Vittorio, Samuel Peña-Díaz, Giovanna Pitasi, Marc Fornt-Suñé, Federica Bucolo, Salvador Ventura, and Rosaria Gitto. 2022. "Ligand-Based Discovery of a Small Molecule as Inhibitor of α-Synuclein Amyloid Formation" International Journal of Molecular Sciences 23, no. 23: 14844. https://doi.org/10.3390/ijms232314844