Concepts and Case Studies in Chemical Biology

Retaining the proven didactic concept of the successful "Chemical Biology - Learning through Case Studies", this sequel features 27 new case studies, reflecting the rapid growth in this interdisciplinary topic over the past few years. Edited by two of the world's leading researchers in the field, this textbook introduces students and researchers to the modern approaches in chemical biology, as well as important results, and the techniques and methods applied. Each chapter presents a different biological problem taken from everyday lab work, elucidated by an international team of renowned scientists. With its broad coverage, this is a valuable source of information for students, graduate students, and researchers working on the borderline between chemistry, biology, and biochemistry.

Table of Contents:
Introduction and Preface Abbreviations REAL-TIME AND CONTINUOUS SENSORS OF PROTEIN KINASE ACTIVITY UTILIZING CHELATION-ENHANCED FLUORESCENCE Introduction The Biological Problem The Chemical Approach Chemical Biological Research/Evaluation Conclusions FLiK AND FLiP: DIRECT BINDING ASSAYS FOR THE IDENTIFICATION OF STABILIZERS OF INACTIVE KINASE AND PHOSPHATASE CONFORMATIONS Introduction - The Biological Problem The Chemical Approach Chemical Biological Research/Evaluation Conclusions STRATEGIES FOR DESIGNING SPECIFIC PROTEIN TYROSINE PHOSPHATASE INHIBITORS AND THEIR INTRACELLULAR ACTIVATION Introduction - The Biological Problem The Chemical Approach Chemical Biological Research/Evaluation Conclusions DESIGN AND APPLICATION OF CHEMICAL PROBES FOR PROTEIN SERINE/THREONINE PHOSPHATASE ACTIVATION Introduction The Biological Problem The Chemical Approach Chemical Biological Research/Evaluation Conclusion AUTOPHAGY: ASSAYS AND SMALL-MOLECULE MODULATORS Introduction The Biological Problem The Chemical Approach Chemical Biological Evaluation Conclusion ELUCIDATION OF PROTEIN FUNCTION BY CHEMICAL MODIFICATION Introduction The Biological Problem The Chemical Approach Biological Research/Evaluation Conclusion INHIBITION OF ONCOGENIC K-Ras SIGNALING BY TARGETING K-Ras-PDEDelta Introduction The Biological Problem The Chemical Approach Chemical Biological Evaluation Conclusions DEVELOPMENT OF ACYL PROTEIN THIOESTERASE 1 (APT1) INHIBITOR PALMOSTATIN B THAT REVERT UNREGULATED H/N-Ras-SIGNALING Introduction The Biological Problem - The Role of APT1 in Ras Signaling The Chemical Approach Chemical Biological Research/Evaluation Conclusions FUNCTIONAL ANALYSIS OF HOST-PATHOGEN POSTTRANSLATIONAL MODIFICATION CROSSTALK OF RAB PROTEINS Introduction The Biological Problem The Chemical Approach Chemical Biological Research/Evaluation Conclusions CHEMICAL BIOLOGY APPROACH TO SUPPRESSION OF STATIN-INDUCED MUSCLE TOXICITY Introduction The Biological Problem The Chemical Approach Chemical Biological Research/Evaluation Conclusion A TARGET IDENTIFICATION SYSTEM BASED ON MORPHOBASE, CHEMPROTEOBASE, AND PHOTO-CROSS-LINKING BEADS Introduction The Biological Problem The Chemical Approach Chemical Biological Research/Evaluation Conclusion ACTIVITY-BASED PROTEASOME PROFILING IN MEDICINAL CHEMISTRY AND CHEMICAL BIOLOGY Introduction The Biological Problem The Chemical Approach Biological Research/Evaluation Conclusions RATIONAL DESIGN OF ACTIVITY-BASED RETAINING BETA-EXOGLUCOSIDASE PROBES Introduction The Biological Problem The Chemical Approach Biological Research/Evaluation Conclusions MODULATION OF ClpP PROTEASE ACTIVITY: FROM ANTIBIOTICS TO ANTIVIRULENCE Introduction The Biological Problem The Chemical Approach The Discovery of a Novel Antibiotic Mechanism The Antivirulence Approach Conclusions AFFINITY-BASED ISOLATION OF MOLECULAR TARGETS OF CLINICALLY USED DRUGS Introduction - The Biological/Medicinal Problem The Chemical Approach Chemical Biological Research Conclusion IDENTIFICATION OF THE TARGETS OF NATURAL-PRODUCT-INSPIRED MITOTIC INHIBITORS Introduction The Biological Problem The Chemical Approach Chemical Biological Evaluation Conclusion FINDING A NEEDLE IN A HAYSTAY. IDENTIFICATION OF TANKYRASE, A NOVEL THERAPEUTIC TARGET OF THE WNT PATHWAY USING CHEMICAL GENETICS Introduction The Biological Problem The Chemical Approach Chemical Biological Research/Evaluation Conclusion THE IDENTIFICATION OF THE MOLECULAR RECEPTOR OF THE PLANT HORMONE ABSCISIC ACID Introduction The Biological Problem The Chemical Genetics Approach The Chemical Biology Approach Conclusion CHEMICAL BIOLOGY IN PLANTS: FINDING NEW CONNECTIONS BETWEEN PATHWAYS USING THE SMALL MOLECULE SORTIN 1 Introduction The Biological Problem The Chemical Approach Biological Research/Evaluation Conclusion SELECTIVE TARGETING OF PROTEIN INTERACTIONS MEDIATED BY BET BROMODOMAINS Introduction The Biological Problem The Chemical Approach Chemical Biological Investigations Conclusion THE IMPACT OF DISTANT POLYPHARMACOLOGY IN THE CHEMICAL BIOLOGY OF PARPS Introduction The Biological Problem The Chemical Approach Chemical Biological Research/Evaluation Conclusions SPLICING INHIBITORS: FROM SMALL MOLECULE TO RNA METABOLISM Introduction The Biological Problem The Chemical Approach Chemical Biological Research/Evaluation Conclusion PHOTOCHEMICAL CONTROL OF GENE FUNCTION IN ZEBRAFISH EMRYOS WITH LIGHT-ACTIVATED MORPHOLINOS Introduction The Biological Problem The Chemical Approach Chemical Biological Research/Evaluation Conclusion LIFE CELL IMAGING OF mRNA USING PNA FIT PROBESIntroduction The Biological Problem The Chemical Approach Chemical Biological Research/Validation Conclusion TARGETING THE TRANSCRIPTIONAL HUB BETA-CATENIN USING STAPLED PEPTIDES Introduction The Biological Problem The Chemical Approach: Hydrocarbon Peptide Stapling The Biological Approach: Phage-Display-Based Optimization Biochemical and Biological Evaluation Conclusions DIVERSITY-ORIENTED SYNTHESIS: DEVELOPING NEW CHEMICAL TOOLS TO PROBE AND MODULATE BIOLOGICAL SYSTEMS Introduction The Biological Problem The Chemical Approach Chemical Biology Research Conclusion SCAFFOLD DIVERSITY SYNTHESIS WITH BRANCHING CASCADES STRATEGY Introduction The Biological/Pharmacological Problem: Discovering Small Bioactive Molecules The Chemical Approach: Scaffold Diversity Chemical/Biological Evaluation - Branching Cascades Strategy in Scaffold Diversity Synthesis Conclusions Index

About the Author :
Herbert Waldmann obtained his PhD in organic chemistry from the University of Mainz, Germany, in 1985 working with Professor H. Kunz, after which he completed a postdoctoral appointment with Professor G. Whitesides at Harvard University (USA). He was appointed as Professor of Organic Chemistry at the University of Bonn (1991), full Professor of Organic Chemistry at the University of Karlsruhe (1993), and Director at the Max-Planck-Institute of Molecular Physiology Dortmund and Professor of Organic Chemistry at the University of Dortmund, Germany, in 1999. He has received numerous awards, e.g. the Otto-Bayer-Award (2001), the Max Bergmann Medal (2003), and recently the Emil-Fischer-Prize (2012). His research interests lie in bioactive compound development, target identification, and the chemical biology of Ras proteins. Petra Janning studied chemistry at the University of Munster, Germany, and did her PhD thesis at the Institute for Analytical Sciences in Dortmund, Germany in 1995. After different positions where she worked in the area of analytical chemistry and on the borderline between chemistry and biology she joined the Max-Planck-Institute of Molecular Physiology, Dortmund, in the department of Professor H. Waldmann, where she is currently working. She is responsible for the Bioorganic Practical Course and the analytics in the department. She focused her work on mass spectrometry based methods in proteome research in particular in target protein identification of small molecules.