首页 > 新书资源
新书资源(2012年11月)

New frontiers in chemical biology : enabling drug discovery / edited by Mark E. Bunnage. — Cambridge, UK : RSC Pub., c2011. – (63.32/N532n)

Contents

    Contents
    
    Chapter 1 The Chemical Genetic Approach: The Interrogation of Biological Mechanisms with Small Molecule Probes
    1.1 Introduction to Chemical Genetics
     1.1.1 Forward and Reverse Chemical Genetics
     1.1.2 Screening Small Molecule Libraries: Some General Considerations
    1.2 Synthetic Strategies for Exploring Biologically Relevant Chemical Space
     1.2.1 Synthesis of Compound Libraries with High Substitutional Diversity
     1.2.2 Synthesis of Compound Libraries with High Stereochemical Diversity
     1.2.3 Synthesis of Compound Libraries with High Scaffold Diversity
     1.2.4 Emerging Approaches for Ligand Discovery Using Large Small Molecule Libraries
    1.3 Discovery of Small Molecule Probes
     1.3.1 Discovery of Small Molecule Probes Using a Reverse Chemical Genetic Approach
     1.3.2 The Forward Chemical Genetic Approach
    1.4 Case Study: Interrogation of the Sonic Hedgehog Pathway Using Complementary Small Molecule Probes
    1.5 Summary and Outlook
    References
    Chapter 2 Applications for Activity-based Probes in Drug Discovery
    2.1 Background
     2.1.1 Introduction
     2.1.2 Activity-based Probes
    2.2 Applications of Activity-based Probes to Drug Discovery
     2.2.1 Identification and Validation of Drug Targets Using Activity-based Probes
     2.2.2 Use of Activity-based Probes for Drug Lead Identification and Assessment of Selectivity
     2.2.3 Use of Activity-based Probes for Assessment of In vivo Pharmacodynamic Properties and Efficacy of Lead Compounds
     2.2.4 In vivo Imaging Applications
    2.3 Outlook
    Acknowledgements
    References
    Chapter 3 Targeted Intracellular Protein Degradation as a Potential Therapeutic Strategy
    3.1 Background
     3.1.1 Introduction
     3.1.2 The Ubiquitin-Proteasome System
     3.1.3 Modulation of Protein Levels in Cells
    3.2 Development of the PROTACs Approach
     3.2.1 Initial Proof-of-Concept
     3.2.2 Targeting Tumor-relevant Proteins In vitro and In vivo
     3.2.3 Development of Cell Permeable PROTACs
     3.2.4 Development of an All-small Molecule PROTAC
     3.2.5 Further Exploration of the PROTAC Technique
    3.3 Outlook
     3.3.1 Strengths of the PROTAC Technique
     3.3.2 Potential Applications of the PROTAC Technique
     3.3.3 Continued Development of the PROTAC Technique
    Acknowledgement
    References
    Chapter 4 Chemical Biology of Stem Cell Modulation
    4.1 Introduction
    4.2 Stem Cells: Ontogeny, Characterisation and Clinical Utility
    4.3 Stem Cell Manipulation In Vitro
     4.3.1 Small Molecules to Promote Stem Cell Expansion
     4.3.2 Small Molecules to Direct Stem Cell Differentiation
     4.3.3 Small Molecules to Promote Dedifferentiation and Transdifferentiation
    4.4 Stem Cell Manipulation In Vivo
     4.4.1 Exogenous Stem Cells: Homing, Engraftment and Activation
     4.4.2 Endogenous Stem Cell Manipulation
     4.4.3 Stem Cells in Dysplasia: Cancer and Teratogenicity
    4.5 Conclusions and Future Prospects
    References
    Chapter 5 Chemical Biology of Histone Modifications
    5.1 Histones, Epigenetics and Chromatin
     5.1.1 DNA Modifications
     5.1.2 Euchromatin and Heterochromatin
     5.1.3 Correlation of Histone Modifications with Transcriptional States
     5.1.4 Mechanisms by Which Histone Modifications Achieve Transcriptional Regulation
     5.1.5 Epigenetics
    5.2 The Lysine Acetylation System
     5.2.1 Histone Acetyltransferases
     5.2.2 Histone Deacetylases
     5.2.3 Bromodomains
    5.3 The Lysine and Arginine Methylation System
     5.3.1 Histone Methyltransferases
     5.3.2 Histone Demethylases
     5.3.3 Methyl Binding Domains
    5.4 Serine/Threonine/Tyrosine Phosphorylation of Histones
    5.5 Lysine Ubiquitylation/SUMOylation/Biotinylation of Histones
    5.6 Appendix: Abbreviations Used in this Chapter
    Acknowledgements
    References
    Chapter 6 Chemologies
    6.1 Introduction
    6.2 Synthetic Vaccines
     6.2.1 Carbohydrate-based Vaccines
     6.2.2 Purely Synthetic Vaccines
     6.2.3 Synthetic Virus-like Particles
     6.2.4 Expanding the Genetic Code and Breaking Self-tolerance
     6.2.5 Chemically Programmed Vaccination
    6.3 Antibodies
     6.3.1 Antibody-directed Therapies
     6.3.2 Improved Pharmacokinetics
    6.4 Oligonucleotides
     6.4.1 Aptamers - Macugen
     6.4.2 siRNA
     6.4.3 Locked Nucleic Acids
    6.5 Conclusions
    References and Notes
    Chapter 7 Antibody-Drug Conjugates in Oncology
    7.1 Introduction and General Considerations
    7.2 Calicheamicin Conjugates
    7.3 Maytansine Conjugates
    7.4 Auristatin Conjugates
    7.5 Duocarmycin Conjugates
    7.6 Miscellaneous Conjugates
    7.7 Conclusions
    References
    Chapter 8 Drug Discovery by DNA-encoded Libraries
    8.1 Introduction
     8.1.1 The Lack of Discovery Tools Interrogating Undrugged Targets
     8.1.2 Applying Nature's Strategy in Discovering Functional Molecules
     8.1.3 Topics in this Chapter
    8.2 DNA-templated library
     8.2.1 Basic Principles of DNA-templated Organic Synthesis
     8.2.2 The Development of DNA-templated Libraries
     8.2.3 The Application of DNA-templated Libraries in Drug Discovery
    8.3 DNA-recorded Library
     8.3.1 GSK/Praecis
     8.3.2 Neri Group/Philochem
     8.3.3 A DNA-recorded Library by DNA Assembly: ESAC Library
    8.4 Discussion
     8.4.1 The Advantages of DNA-encoded Library
     8.4.2 Prospects and Outlook
    Acknowledgements
    References
    Subject Index