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Book Cover
E-book
Author Byun, Wan Gi

Title Discovery of small-molecule modulators of protein-RNA interactions for treating cancer and COVID-19 / Wan Gi Byun
Published Singapore : Springer, 2023

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Description 1 online resource (156 p.)
Series Springer Theses
Springer theses.
Contents Intro -- Supervisor's Foreword -- Abstract -- Acknowledgements -- Contents -- List of Figures -- List of Tables -- List of Schemes -- 1 Introduction -- 1.1 Protein-RNA Interaction -- 1.2 Therapeutic Potentials of Modulating PRI -- 1.3 Chemical Biology Approaches for the Discovery of PRI Modulator -- 1.4 Aims and Scope of the Thesis -- References -- 2 Identification of Small-Molecule Inhibitors of Oncogenic Lin28-Let-7 Interaction -- 2.1 Discovery of a Small-Molecule Inhibitor of Protein-microRNA Interaction Using Binding Assay with a Site-Specifically Labeled Lin28 -- 2.1.1 Introduction
2.1.2 Results and Discussion -- 2.1.3 Conclusion -- 2.1.4 Experimental Section -- 2.2 Restoring Let-7 MicroRNA Biogenesis Using a Small-Molecule Inhibitor of the Protein-RNA Interaction -- 2.2.1 Introduction -- 2.2.2 Results and Discussion -- 2.2.3 Conclusion -- 2.2.4 Experimental Section -- References -- 3 Discovery of Small-Molecule Modulators of Protein-RNA Interactions by Fluorescence Intensity-Based Binding Assay -- 3.1 Introduction -- 3.2 Results and Discussion -- 3.2.1 Construction of a Fluorescence Intensity-Based Lin28-Let-7 Binding Assay
3.2.2 Discovery of a New Class of Small-Molecule Inhibitors of the Lin28-Let-7 Interaction -- 3.2.3 Construction of a Fluorescence Intensity-Based Assay to Monitor Roquin-Tnf CDE Interaction -- 3.3 Conclusion -- 3.4 Experimental Section -- 3.4.1 Protein Expression and Purification -- 3.4.2 Fluorescence Intensity-Based Binding Assays -- 3.4.3 Electrophoretic Mobility Shift Assay (EMSA) -- 3.4.4 RNA Sequences -- 3.4.5 TaqMan MiRNA Assay-Based QRT-PCR -- 3.4.6 Cell Culture -- 3.4.7 Western Blot -- 3.4.8 Chemistry -- 3.4.9 Purity Determination from HPLC Analysis
3.4.10 Synthetic Procedures and Spectroscopic Data -- References -- 4 Harnessing Stress Granule Formation by Small Molecules to Inhibit the Cellular Replication of SARS-CoV-2 -- 4.1 Introduction -- 4.2 Results and Discussion -- 4.2.1 Identification of Small-Molecule Enhancers of Stress Granule Formation and Their Cellular Antiviral Activities -- 4.2.2 Inhibition of the Cellular Replication of SARS-CoV-2 by the Stress Granule Enhancers -- 4.3 Conclusion -- 4.4 Experimental Section -- 4.4.1 Chemistry -- 4.4.2 Purity Determination from HPLC Analysis -- 4.4.3 Cell Culture and Transfection
4.4.4 Western Blot -- 4.4.5 Stress Granule Imaging by Immunofluorescence -- 4.4.6 Stress Granule Monitoring and Compound Screening Using G3BP1-GFP Expressed U2OS Cell Line -- 4.4.7 Cell Viability Assay -- 4.4.8 RNA Extraction and Quantitative Real-Time PCR -- 4.4.9 Virus -- 4.4.10 Antiviral Test and Dose-response Curve (DRC) Analysis by Immunofluorescence -- 4.4.11 Co-Immunofluorescence -- 4.4.12 Drug Combination Assay -- 4.4.13 Spectroscopic, Mass & HPLC Purity Data -- References -- Appendix
Summary This book describes the development of novel proteinRNA-binding assays and their applications in a high-throughput manner for the identification of small-molecule modulators of proteinRNA interactions to treat cancer and COVID-19. Modulating proteinRNA interactions with small molecules is expected to provide novel biological insights of the interrelation of diseases with the proteinRNA interactome. The modulations may also be exploited therapeutically. For these reasons, the development of a simple, reliable, and sensitive proteinRNA-binding assay is necessary for high-throughput screening to discover new effective chemical entities capable of acting on diverse proteinRNA interactions. This book discusses the discovery of small-molecule modulators targeting proteinRNA interactions that are potentially valuable to treat cancer and COVID-19 by constructing novel high-throughput screening methods. The results of this dissertation provide valuable insights into the regulation of proteinRNA interactions in chemical biology and drug development
Notes "Doctoral thesis accepted by Seoul National University, Seoul, Korea (Republic of)"
Bibliography Includes bibliographical references
Notes Online resource; title from PDF title page (SpringerLink, viewed January 4, 2023)
Subject RNA-protein interactions.
Cancer -- Genetic aspects.
Cancer -- Molecular aspects.
COVID-19 (Disease) -- Genetic aspects
COVID-19 (Disease) -- Molecular aspects
RNA.
Proteins.
Neoplasms -- therapy
Neoplasms -- genetics
RNA
COVID-19
Proteins
protein.
Cancer -- Genetic aspects
Cancer -- Molecular aspects
RNA-protein interactions
Form Electronic book
ISBN 9789811978142
981197814X