CiNii Books - Combinatorial library methods and protocols

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.

Table of 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

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Combinatorial library methods and protocols

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