Targeting Protein-Protein Interactions for Drug Discovery
1. Auflage November 2025
432 Seiten, Hardcover
24 Abbildungen (24 Farbabbildungen)
11 Tabellen
Monographie
Kurzbeschreibung
Provides comprehensive up-to-date information on current topics in protein-protein interaction drug discovery.
Up-to-date reference surveying the latest advances in the structural understanding of protein-protein interactions and developments in drug discovery and therapeutics
Targeting Protein?Protein Interactions for Drug Discovery provides a systematic and comprehensive overview of protein-protein interactions (PPIs), reviewing foundational concepts, advanced methodologies, and emerging therapeutic strategies, reflecting the multidisciplinary nature of PPI research.
This book discusses computational methods for predicting PPI structures, with a special emphasis on protein docking and deep learning-based approaches, diverse chemical scaffolds for PPI modulation, including foldamers as inhibitors of aberrant PPIs and sulfonyl-¿-AApeptides as novel modulators, and the development and application of stapled peptides as modulators of intracellular PPIs, offering enhanced stability, binding affinity, and cellular permeability.
Readers will also find information on cyclic peptides, focusing on their unique conformational stabilization and therapeutic potential across a range of diseases, small molecule inhibitors targeting BCL-family proteins, revealing their potential in cancer therapy, molecular glues as activators for PPIs, categorized into degraders, stabilizers, and inhibitors based on their biological effects, and the targeting of the APC?Asef interaction for drug discovery in colorectal cancer therapy, offering a case study of specificity and clinical relevance.
Targeting Protein?Protein Interactions for Drug Discovery explores sample topics including:
* Challenges and strategies of drug discovery targeting PPIs, including high-throughput screening and structure-based drug design
* Fluorescence resonance energy transfer (FRET) technology, a powerful tool for real-time analysis of molecular interactions in live cells
* Utility of mass spectrometry (MS) for large-scale mapping of PPI networks with high sensitivity and resolution
* Proximity ligation assays (PLA) for detecting PPIs in situ, emphasizing spatial precision and adaptability for multiplexed detection
* Application of surface plasmon resonance (SPR) for characterizing PPI specificity, affinity, and kinetics
Exploring both classical and novel approaches to PPI characterization and modulation, Targeting Protein?Protein Interactions for Drug
Discovery offers a comprehensive reference for researchers aiming to unlock the therapeutic potential of PPIs along with educators and students engaged in the study of cellular mechanisms, drug discovery, and biotechnology.
1.1 General concepts of protein-protein interactions
1.2 Functional significance of protein-protein interactions
1.3 Methods for analyzing protein-protein interactions
1.4 Implications of the basic research on protein-protein interactions
1.5 Conclusions and perspectives
Chapter 2: Overview of drug discovery targeting PPI systems
2.1 Introduction
2.2 Fundamentals of Protein-Protein Interactions
2.3 Challenges in Targeting PPI Systems
2.4 Approaches in Drug Discovery Targeting PPI Systems
2.5 Case Studies and Success Stories
2.6 Conclusion
Chapter 3: Fluorescence Resonance Energy Transfer Technology and its Applications
3.1 Introduction
3.2 Mechanism of FRET
3.3 Applications of FRET
3.4 Advantages and Limitations
3.5 Recent Advances
3.6 Conclusion
Chapter 4: Dissect Protein Interactions Using Mass Spectrometry
4.1 Introduction
4.2 Affinity purification coupled with mass spectrometry (AP-MS)
4.3 Proximity labeling
4.4 Cross-linking mass spectrometry (XL-MS)
4.5 Co-fractionation coupled with mass spectrometry (CF-MS)
4.6 Thermal proximity coaggregation (TPCA)
4.7 Limited proteolysis?mass spectrometry (LiP?MS)
4.8 Conclusion and outlook
Chapter 5: Detection of protein-protein interactions in situ via proximity ligation assay
5.1 Introduction
5.2 Implementations of proximity ligation assay
5.3 Applications of PLA for detecting protein-protein interactions
5.4 Conclusions and outlooks
Chapter 6: The Application of Surface Plasmon Resonance in the Characterization of Protein-Protein Interactions
6.1 Introduction
6.2. Applications of SPR assay in PPI Characterization
6.3. Advantages and Limitations of SPR Application for PPIs
6.4. Future Directions
Chapter 7: Computational methods for protein-protein interactions
7.1. Introduction
7.2. Protein-protein docking
7.3. End-to-end structure prediction
7.4. CAPRI experiments
7.5. Challenges and Future directions
Chapter 8: Foldamers as Inhibitors of Aberrant Protein-Protein Interactions
8.1 Introduction
8.2 The Evolution of Hamilton?s Oligopyridylamides
8.3 Limitations of a Tedious Synthetic Route
8.4 OPs as Antagonists of Neurodegeneration
8.5 OPs Inhibit HIV Infection
8.6 OPs Targeting Type II Diabetes
8.7 OPs Targeting and Reactivating Mutant Protein in Cancer
8.8 Novel Synthesis of OPs and Alzheimer?s Disease
8.9 2D-FAST
8.10 OQ Foldamers - Structure and Discovery
8.11 Synthesis of OQ Foldamers
8.12 OQs as Modulators of Type II Diabetes-Related aPPIs
8.13 Mechanistic Insights to OQ Manipulation of aPPIs
8.14 Chemical Diversity and Structure Modulate Efficacy of Oqs
8.15 Modulation of Alzheimer?s Disease-Related Aß
8.16 OQs for the Modulation of Synucleinopathies
8.17 Epilogue
Chapter 9: Application of Sulfonyl-¿-AApeptides for PPI Drug Discovery
9.1 Introduction to the Structure of Sulfonyl-¿-AA-peptides
9.2 The Applications of Sulfonyl-¿-AA-peptides
9.3 Future Directions/Conclusions
Chapter 10: Introduction of the Application of Stapled Peptides in Protein-Protein Interactions Drug Discovery and their Successful Examples
10.1. Introduction
10.2. Stapled Peptides: Structure Features and Benefits
10.3. Successful Applications of Stapled Peptides in Drug Discovery
10.4. Challenges and Limitations
10.5. Future Directions
Chapter 11: Cyclic peptides for PPI drug discovery
11.1. a-helix cyclic peptides (stapled peptides)
11.2. ß-hairpin cyclic peptides
11.3. Macrocyclic peptides
11.4. Summary and outlook
Chapter 12: Small molecule inhibitors targeting protein-protein interactions in the BCL protein
12.1 Introduction
12.2 Inhibitors of BCL-2 family antiapoptotic proteins
12.3 Inhibitors of ß-catenin/BCL9
12.4 Targeting BCL-6 small molecule inhibitors
12.5. BCL-3 inhibitors
12.6. BCL-10 inhibitors
12.7. Summary
Chapter 13: Molecular Glues as Activators for PPI
13.1 Introduction
13.2 Molecular Glues as orthosteric PPI stabilizers/activators
13.3 Methods for Molecular Glue Discovery
13.4 Conclusions and Outlook
Chapter 14: Targeting APC?Asef Protein-Protein Interaction for Drug Discovery in Colorectal Cancer Therapy
14.1. Introduction
14.2. Structural insights into APC?Asef interaction
14.3. Current APC?Asef inhibitor
14.4. A More Sensitive FP Method for Identifying Highly Active APC?Asef Inhibitors
14.5. Conclusions and Outlook
Chapter 15: Computational methods applied to drug discovery of protein-protein interaction systems
15.1 Introduction
15.2 Computational methods for PPI prediction
15.3 Conclusions and outlook