BIO-NMR IN DRUG RESEARCH

BioNMR spectroscopy offers a universal tool for examining the binding of an active substance to its target protein. Its use thereby benefits the rational development of drugs. This interaction can now be investigated in a hitherto unparalleled precision and displayed in 3D—an important prerequisite for the targeted development of new active substances. The latest methods for characterizing substance-receptor complexes are demonstrated backed by many case studies from pharmaceutical research. Thus it comes as no surprise that a large number of the authors are working for leading pharmaceutical companies.

With its successful mixture of basic information and application strategies, coupled with many real-life examples, this is an invaluable guide for both NMR spectroscopists and pharmaceutical researchers.

Oliver Zerbe was born in 1963 and studied chemistry at the University of Hamburg, Germany, and in Southampton, UK. He received his Ph.D. in 1994 in organic chemistry from the University in Zurich under the supervision of Wolfgang von Philips born in the field of NMR methodology as applied to peptides.

From 1994 to 1995 he we was a postdoc with Kurt Wuthrich at the Federal Technical University of Switzerland (ETH) working on the design of pulse sequences for isotopic ally labeled proteins. He received his habilitation in medicinal chemistry from the Institute of Pharmaceutical Sciences, ETH Zurich, in 2004 under the guidance of Gerd Folkers. Oliver Zerbe is presently head of the NMR facilities and lecturer of the Institute of Organic Chemistry of the University of Zurich where he became a Privatdozent in 2005 and Titular professor in 2008.

Foreword.

List of Authors.

List of Abbreviations.

PART I: BASIC TECHNIQUES.

Modern Methods for the Expression of Proteins in Isotopically Enriched Form (H. Patzelt, et al.).

Structure Calculation Using Automated Techniques (P. Güntert).

Achieving Better Sensitivity, Less Noise and Fewer Artifacts in NMR Spectra (D. Moskau & O. Zerbe).

PART II: NMR OF BIOMOLECULES.

NMR Strategies for Protein Assignments (V. Dötsch).

NMR of Membrane-Associated Peptides and Proteins (R. Bader, et al.).

NMR of Nucleic Acids (R. Fiala & V. Sklenár).

PART III MODERN SPECTROSCOPIC TECHNIQUES.

Methods for the Measurement of Angle Restraints from Scalar, Dipolar Couplings from Cross-Correlated Relaxation: Application to Biomacromolecules (C. Griesinger).

Orientational Restraints (E. de Alba & N. Tjandra).

Scalar Coupling Across Hydrogen Bonds (A. Dingley, et al.).

TROSY: Transverse Relaxation-Optimized Spectroscopy (R. Riek).

MAS Solid-State NMR of Isotopically Enriched Biological Samples (P. Williamson , et al.).

Determination of Protein Dynamics Using ¹⁵N Relaxation Measurements (D. Fushman).

PART IV: TOOLS FOR INVESTIGATION OF DRUG - RECEPTOR COMPLEXES AND FOR LIGAND SCREENING.

The Determination of Equilibrium Dissociation Constants of Protein-Ligand Complexes by NMR (G. Roberts).

Experiments in NMR-Based Screening (C. Marchioro, et al.).

The Use of Spin Labels in NMR-Supported Lead Finding and Optimization (W. Jahnke).

NMR of Weakly Binding Ligands (M. Blommers & S. Rüdisser).

Isotope Filter and Editing Techniques (G. Gemmecker).

PART V: STRATEGIES FOR DRUG DEVELOPMENT USING NMR.

Strategies for NMR Screening and Library Design (C. Lepre).

Strategies for Hit Finding Using NMR (W. Klaus & H. Senn).

Strategies for Drug Discovery Using NMR (M. Blommers, et al.).

NMR-Based Drug Design: Approaches for Very Large Proteins (M. Pellecchia, et al.).

Subject Index.