Chapter 1. Introduction............................................................................ 1
1.1. Protein-RNA interaction.............................................................. 1
1.2. Therapeutic potentials of modulating PRI.................................... 1
1.3. Chemical biology approaches for the discovery of PRI modulator
............................................................................................................. 3
1.4. Aims and scope of the thesis........................................................ 5
1.5. References.................................................................................... 5
Chapter 2. Identification of Small-Molecule Inhibitors of Oncogenic Lin28-Let-7 Interaction 8
2.1. Discovery of a small-molecule inhibitor of protein-microRNA interaction using binding assay with a site-specifically labeled Lin28..................................................................... 8
2.1.1. Introduction..................................................................... 8
2.1.2. Results and discussion................................................... 11
2.1.3. Conclusion..................................................................... 26
2.1.4. Experimental section..................................................... 27
2.1.5. References..................................................................... 37
2.2. Restoring let-7 microRNA biogenesis using a small-molecule inhibitor of the protein-RNA interaction................................................................................................................... 41
2.2.1. Introduction................................................................... 41
2.2.2. Results and discussion................................................... 43
2.2.3. Conclusion..................................................................... 53
2.2.4. Experimental section..................................................... 53
2.2.5. References..................................................................... 58
Chapter 3. Discovery of Small-Molecule Modulators of Protein-RNA Interactions by Fluorescence Intensity-Based Binding Assay............................................................... 61
3.1. Introduction................................................................................ 61
3.2. Results and discussion................................................................ 63
3.3. Conclusion.................................................................................. 76
3.4. Experimental section.................................................................. 76
3.5. References.................................................................................. 85
Chapter 4. Identification of Protein-RNA Interaction Modulators for Treating COVID-19 88
4.1. Harnessing stress granule formation by small molecules to inhibit the cellular replication of SARS-CoV-2......................................................................................................... 88
4.1.1. Introduction................................................................... 88
4.1.2. Results and discussion................................................... 89
4.1.3. Conclusion................................................................... 103
4.1.4. Experimental section................................................... 104
4.1.5. References.................................................................... 110
4.2. Discovery of a small-molecule degrader of SARS-CoV-2 Nsp1 by autophagic pathway
