BioNMR in Drug Research

Der kürzlich an Kurt Wüthrich verliehene Nobelpreis für die Methode der BioNMR trägt den großen Fortschritten in der Untersuchung von Biomolekülen durch NMR Rechnung. Herausgegeben von einem ehemaligen Mitarbeiter Wüthrichs, präsentiert dieses Buch die theoretischen Grundlagen zur BioNMR neben deren Einsatzmöglichkeiten zur Strukturaufklärung von Proteinen und Nucleinsäuren. Mit der BioNMR steht nicht zuletzt ein universell einsetzbares Werkzeug zur Untersuchung der Bindung eines Wirkstoffs an sein Zielprotein zur Verfügung, von dessen Einsatz insbesondere die Arzneistoffentwicklung profitiert. Diese Wechselwirkung kann heute mittels NMR in unübertroffener Genauigkeit untersucht und räumlich dargestellt werden; eine wichtige Vorbedingung für die gezielte Entwicklung von neuen Wirkstoffen. Neueste Techniken zur Charakterisierung von Wirkstoff-Rezeptor-Komplexen werden vorgestellt und mit vielen Fallstudien aus der Pharmaforschung untermauert.
Es ist daher nicht verwunderlich, dass ein großer Teil der Autoren dieses Buches bei führenden Pharmaunternehmen tätig ist. Mit einer gelungenen Kombination aus Grundlagenwissen und Anwendungsstrategien, inklusive vieler Beispiele aus der Praxis, ist dieses Werk für den NMR-Spektroskopiker wie für den Pharmaforscher ein unentbehrlicher Leitfaden für das aufstrebende Gebiet der BioNMR in der Arzneistoffentwicklung.

Auteur

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 Wüthrich 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.

Résumé
The vast progress made in the investigation of biomolecules using NMR has only recently been rewarded with the Nobel Prize for Kurt Wuthrich. Edited by a former coworker of Wuthrich, this book presents the theoretical background on NMR of biomolecules, plus the use of NMR techniques in determining the structures of proteins and nucleic acids.
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.

Contenu
BASIC TECHNIQUES
Modern Methods for Expression of Proteins in Isotopically Enriched Form
Structure Calculation Using Automated Techniques
Achieving Better Sensitivity, Less Noise and Less Artifacts in NMR Spectra

NMR OF BIOMOLECULES
NMR Strategies for Protein Assignment
NMR of Membrane-Associated Peptides and Proteins
NMR of Nucleic Acids

MODERN SPECTROSCOPIC TECHNIQUES
Methods for the Measurement of Angle Restraints from Scalar and Dipolar Couplings as well as from Cross Correlated Relaxation: Application to Biomolecules
Orientational Restraints
Scalar Coupling Across Hydrogen Bonds
TROSY:Transverse Relaxation-Optimized Spectroscopy
MAS Solid-State NMR of Isotopically Enriched Biological Samples
Determination of Protein Dynamics Using 15N Relaxation Measurements

TOOLS FOR INVESTIGATION OF DRUG-RECEPTOR COMPLEXES AND FOR LIGAND SCREENING
The Determination of Equilibrium Dissociation Constants of Protein-Ligand Complexes by NMR
Experiments in NMR-based Screening
The Use of Spin-Labels in NMR-supported Lead Finding and Optimization
NMR of Weakly Binding Ligands
Isotope Filter and Editing Techniques

STRATEGIES FOR DRUG DEVELOPMENT USING NMR
Strategies for NMR Screening and Library Design
Strategies for Hit Finding Using NMR
Strategies for Drug Discovery Using NMR
NMR-based Drug Design: Approaches for Very Large Proteins