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Main description:
The continued successes of large- and small-scale genome sequencing projects are increasing the number of genomic targets available for drug d- covery at an exponential rate. In addition, a better understanding of molecular mechanisms-such as apoptosis, signal transduction, telomere control of ch- mosomes, cytoskeletal development, modulation of stress-related proteins, and cell surface display of antigens by the major histocompatibility complex m- ecules-has improved the probability of identifying the most promising genomic targets to counteract disease. As a result, developing and optimizing lead candidates for these targets and rapidly moving them into clinical trials is now a critical juncture in pharmaceutical research. Recent advances in com- natorial library synthesis, purification, and analysis techniques are not only increasing the numbers of compounds that can be tested against each specific genomic target, but are also speeding and improving the overall processes of lead discovery and optimization. There are two main approaches to combinatorial library production: p- allel chemical synthesis and split-and-mix chemical synthesis. These approaches can utilize solid- or solution-based synthetic methods, alone or in combination, although the majority of combinatorial library synthesis is still done on solid support. In a parallel synthesis, all the products are assembled separately in their own reaction vessels or microtiter plates. The array of rows and columns enables researchers to organize the building blocks to be c- bined, and provides an easy way to identify compounds in a particular well.
Contents:
Part I. Library Synthesis and Quality Control
Using a Noncovalent Protection Strategy to Enhance Solid-Phase Synthesis
Fahad Al-Obeidi, John F. Okonya, Richard E. Austin, and Dan R. S. Bond
Quality Control of Solid-Phase Synthesis by Mass Spectrometry
Jean-Louis Aubagnac, Robert Combarieu, Christine Enjalbal, and Jean Martinez
Preparation of Encoded Combinatorial Libraries for Drug Discovery
Tao Guo and Doug W. Hobbs
Simple Tools for Manual Parallel Solid Phase Synthesis
Viktor Krchnak and Andrew Burritt
Cleavage of Compounds from Solid Phase by Gaseous Reagents
Viktor Krchnak
Synthesis of DNA-Binding Polyamides: Robust Solid-Phase Methods for Coupling Heterocyclic Aromatic Amino Acids
Peter O. Krutzik and A. Richard Chamberlin
The Preparation of Phenyl-stilbene Derivatives Using the Safety Catch Linker
Amy Lew and A. Richard Chamberlin
Host-Guest Chemistry: Combinatorial Receptors
Brian R. Linton
Automated Structure Verification of Small Molecules Libraries Using 1D and 2D NMR Techniques
Gerard Rosse, Peter Neidig, and Harald Schroeder
Rapid Liquid-Phase Combinatorial Synthesis of Heterocyclic Libraries
Chung-Ming Sun
Soluble Polymer-Supported Methods for Combinatorial and Organic Synthesis
Paul Wentworth, Jr. and Carsten Spanka
Analytical Methods for Optimization and Quality Control of Combinatorial Synthesis
Bing Yan, Liling Fang, Mark M. Irving, Jiang Zhao, Diana Liu, Gianine M. Figliozzi, Frank Woolard, and Clinton A. Krueger
Part II. Library Purification and Screening
Resolving Racemic Mixtures Using Parallel Combinatorial Libraries
Tingyu Li, Yan Wang, and Louis H. Bluhm
Ligand Libraries for the Extraction of Metal Ions: Dynamic Combinatorial and High-Throughput Screening Methods
Seema Choudhary and Janet R.Morrow
Automated Liquid-Liquid Extraction and Ion-Exchange Solid-Phase Extraction for Initial Purification
Sean X. Peng and Charles Henson
On-Bead and Solution Screening Approaches for Genomically Derived Targets: Discovery of Surrogate Ligands and Substrates Using Combinatorial Chemistry Libraries
David S. Thorpe, Gerard Rosse, Helen Yeoman, Sydney Wilson, Patti Willson, Greg Harlow, Anna Robinson, and Kenneth F. Wertman
Part III. Computational Library Design
Design of Virtual Combinatorial Libraries
Alex M. Aronov
Approaches to Library Design for Combinatorial Chemistry
Stefan Gussregen, Bernd Wendt, and Mark Warne
Reagent-Based and Product-Based Computational Strategies in Library Design
Eric A. Jamois
Designing Combinatorial Libraries for Efficient Screening
John I. Manchester and David S. Hartsough
Application of Neural Networks to Large Dataset QSAR, Virtual Screening, and Library Design
David A. Winkler and Frank R. Burden
Index
PRODUCT DETAILS
Publisher: Springer (Humana Press Inc.)
Publication date: September, 2013
Pages: 385
Weight: 584g
Availability: Available
Subcategories: Biochemistry
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