دانلود کتاب Advances in Combinatorial Chemistry and High Throughput Screening: Volume 1

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Cover
Advances in Combinatorial Chemistry and High Throughput Screening: Volume 1
Copyright
Contents
Foreword
Preface
List of Contributors
1. Assessing Chemicals Using Partial Order Ranking Methodology
1. Introduction
2. Methods
2.1. Partial Order Ranking
2.2. Linear Extensions
2.3. Average Ranks
2.5. Hierarchical POR
2.6. Accumulating Partial Order Ranking
2.6.1. Probabilities Based on Accumulated Ranks
2.7. Quantitative Structure-Activity Relationships
3. Results
3.1. The Simple Approach
3.2. Relative Descriptor Importance
3.3. Hierarchical Partial Order Ranking
3.4. Accumulating Partial Order Ranking
4. Discussion
5. Conclusions and Outlook
Acknowledgement
Conflict of Interest
Disclosure
References
2. Building a Chemical Space Based on Fragment Descriptors
Abstract
1. Introduction
2. Types of Fragment Descriptors
3. Application of Fragment Descriptors in Virtual Screening and in Silico Design
3.1. Filtering
3.2. Similarity Search
3.3. SAR/QSAR/QSPR Models
3.4. In Silico Design
Conclusion
Acknowledgement
Conflict of Interest
Disclosure
References
3. Fluorescent Probes for Cellular Assays
Abstract
Introduction
Kinases
GPCRs
Ion Channels
Cellular Pathway Analysis
Multiplexing
Conclusion
Acknowledgement
Conflict of Interest
Disclosure
References
4. Label-Free Cell Phenotypic GPCR Drug Discovery
Ye Fang*
Abstract
GPCR Signals
GPCR Oligomerization
Ligand-Directed Functional Selectivity
Label-Dependent Cell-Based Assays
Assays to Measure Changes in Second Messenger
Assays to Measure Protein Trafficking
Assays to Measure Protein-Protein Interaction
Assays to Measure Changes in Gene Reporter Activity
Assays to Measure Changes in Phenotype
Label-Free Cell-Based Assays
RWG Biosensors and Systems
Electrical Biosensors and Systems
Optical Signals of GPCR Activation with RWG Biosensor
Bioimpedance Signals of GPCR Activation
Label-Free Cell-Based Assays for GPCR Screening
Receptor Panning
Systems Cell Biology Studies of GPCR Signaling
Ligand Pharmacological Profiling
High Throughput Screening
Choise of Assay Platforms for GPCR Screening
Conclusion
Acknowledgement
Conflict of Interest
Disclosure
References
5. Immunological Assays: Biotools for High Throughput Screening and Characterisation of Combinatorial Libraries
Abstract
Introduction
The Antibody Molecule
Antibody Engineering
Genetic and Combinatorial Tools
BIological Combinatorial Libraries
Phage Display
Yeast Surface Display
Chemical Combinatorial Libraries
Peptides
Biomimetic Ligands
Immunological Methods
HTS Tools for the Selection of Lead Ligands
ELISA-Based Methods
Conclusion
Abbreviations
Acknowledgement
Conflict of Interest
Disclosure
References
6. Screening and Mechanism-Based Evaluation of Estrogenic Botanical Extracts
Abstract
Introduction
Materials and Methods
Plant Material
Extraction
ER and ER Competitive Binding Assays
Cell Culture Conditions
Induction of Alkaline Phosphatase in Cultured Ishikawa Cells
Cytotoxicity Assay
Measure of ERE Activation
Results
ER Alpha and ER Beta Competitive Assay
Estrogenic Alkaline Phosphatase Induction in the Ishikawa Cell Line
ERE-Luciferase Induction in ER Alpha and ER Beta Positive Cell Lines
Discussion
Abbreviations
Acknowledgement
Conflict of Interest
Disclosure
References
7. A Homogeneous Platform to Discover Inhibitors of the GoLoco Motif/G-alpha Interaction
Abstract
Introduction
Materials and Methods
Chemicals and Assay Material
Protein Expression and Purification
Peptide Synthesis
Fluorescence Polarization Measurements in 96-Well and 384-Well Plate Formats
Surface Plasmon Resonance (SPR) Binding Assay
qHTS Validation in 1,536-Well Plate Format
Results
Detection of G /GoLoco Motif Interactions Using Fluorescence Polarization
Competitive Binding Studies
Estimation of Screening Window
Initial Small Molecule Screen in 96-Well Plate Format
Screening in the 384-Well Plate Format and Hit Validation by SPR
Assay Miniaturization to 1,536-Well Plates and Evaluation of Red-Shifted Peptide Probes
qHTS Robotic Validations Using the LOPAC1280 Library
Discussion
Sensitivity of Binding Detection and Screening Window Optimization
Small-Scale Library Screens and Strategies for Minimizing Compound Interference
Benefits of the qHTS Approach
Acknowledgement
Conflict of Interest
Data Deposition
Disclosure
References
8. G-Protein Activation State-Selective Binding Peptides as New Tools for Probing Heterotrimeric G-protein Subunit Signaling Dynamics
Abstract
Introduction
Screening Methods
Biochemical Insights
KB-752 – a Gα ·GDP-Selective Phage-Display Peptide
KB-1753 and Two Other Peptide Families with Affinity for Activated Gα Subunits
Derivatives of the GoLoco Motif
Gβγ-Interacting Peptides
Structural Insights
KB-752/Gαi1·GDP Complex
KB-1753/Gαi1·GDP·AlF4- Complex
SIGK/Gβ1γ2 Complex
Application in High-Throughput Screening for GPCR Modulators
Concluding Remarks
Abbreviations
Acknowledgement
Conflict of Interest
Disclosure
References
Index
A
B
C
D
E
F
G
H
I
K
L
M
N
O
P
Q
R
S
T
U
V
X
Y