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Synthesis and evaluation of inducers of methuotic cell death and preliminary identification of their cellular targets in glioblastoma cells
Contents
Abstract
Acknowledgments
Contents
1. Current Challenges in Glioblastoma Therapy
1.1 Genetic Alterations and Apoptosis in Glioblastoma
1.2 Methuosis: A Novel Form of Non-Apoptotic Cell Death
2. Synthesis and Evaluation of Indole-Based Chalcones as Inducers of Methuosis, a Novel Type of Nonapoptotic Cell Death
2.1 Introduction
2.2 Results
2.2.1 Structure Activity Relationships
2.2.2 Biological Activity of Compound 19 (MOMIPP) vs.Compound 2 (MIPP)
2.3 Discussion
2.4 Methods
3. Identifying the Target of Methuosis-Inducing Small Molecules
3.1 Current Approaches in Small Molecule Target Identification
3.2 Results
3.2.1 Attempts at MOMIPP Target Enrichment Using In-Situ Click-Chemistry
3.2.2 Attempts at MOMIPP Target Enrichment Using Biotinylated Methuosis-Inducing Derivatives
3.2.3 Preliminary MOMIPP Target Identification Using Photoaffinity Probes
3.2.3.1 Synthesis and Evaluation of Methuosis-Inducing Activity of Photoaffinity Probes
3.2.3.2 Evaluation of 5-Azido-MIPP’s Photoaffinity Properties
3.2.3.3 Evaluation of the Activity of 5-Azido-MIPP Irradiation Products
3.2.3.4 Photoaffinity Labeling of Glioblastoma Cell Lysate
3.3 Discussion
3.3.1 Potential Targets
3.3.2 Limit of Detection
3.4 Methods
4. Summary and Future Work
5. Key Accomplishments
References
Appendices
A Chemistry Experimental Details, Chapter 2
B Chemistry Experimental Details, Chapter 3
C Full protein table associated with Table 3.1
D Additional images associated with Figure 3-21
E Spectra associated with Chapter 2 & 3 Bài viết liên quan
