Main description:

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.

Contents:

List of Contributors XVII Introduction and Preface XXV Abbreviations XXIX 1 Real-Time and Continuous Sensors of Protein Kinase Activity Utilizing Chelation-Enhanced Fluorescence 1 Laura B. Peterson and Barbara Imperiali 1.1 Introduction 1 1.2 The Biological Problem 1 1.3 The Chemical Approach 3 1.4 Chemical Biological Research/Evaluation 12 1.5 Conclusions 14 References 15 2 FLiK and FLiP: Direct Binding Assays for the Identification of Stabilizers of Inactive Kinase and Phosphatase Conformations 17 Daniel Rauh and Jeffrey R. Simard 2.1 Introduction The Biological Problem 17 2.2 The Chemical Approach 20 2.3 Chemical Biological Research/Evaluation 23 2.4 Conclusions 34 References 35 3 Strategies for Designing Specific Protein Tyrosine Phosphatase Inhibitors and Their Intracellular Activation 37 Birgit Hoeger and Maja Kohn 3.1 Introduction The Biological Problem 37 3.2 The Chemical Approach 41 3.3 Chemical Biological Research/Evaluation 45 3.4 Conclusions 47 References 48 4 Design and Application of Chemical Probes for Protein Serine/Threonine Phosphatase Activation 51 YansongWang and Maja Kohn 4.1 Introduction 51 4.2 The Biological Problem 52 4.3 The Chemical Approach 54 4.4 Chemical Biological Research/Evaluation 57 4.5 Conclusion 60 References 60 5 Autophagy: Assays and Small-Molecule Modulators 63 Gemma Triola 5.1 Introduction 63 5.2 The Biological Problem 65 5.3 The Chemical Approach 68 5.4 Chemical Biological Evaluation 71 5.5 Conclusion 80 References 80 6 Elucidation of Protein Function by Chemical Modification 83 Yaowen Wu and Lei Zhao 6.1 Introduction 83 6.2 The Biological Problem 84 6.3 The Chemical Approach 88 6.4 Biological Research/Evaluation 97 6.5 Conclusion 103 References 103 7 Inhibition of Oncogenic K-Ras Signaling by Targeting K-Ras PDE Interaction 105 Gemma Triola 7.1 Introduction 105 7.2 The Biological Problem 105 7.3 The Chemical Approach 108 7.4 Chemical Biological Evaluation 113 7.5 Conclusions 120 References 121 8 Development of Acyl Protein Thioesterase 1 (APT1) Inhibitor Palmostatin B That Revert Unregulated H/N-Ras Signaling 123 Frank J. Dekker, Nachiket Vartak, and Christian Hedberg 8.1 Introduction 123 8.2 The Biological Problem The Role of APT1 in Ras Signaling 123 8.3 The Chemical Approach 125 8.4 Chemical Biological Research/Evaluation 130 8.5 Conclusions 136 References 138 9 Functional Analysis of Host Pathogen Posttranslational Modification Crosstalk of Rab Proteins 141 Christian Hedberg, Roger S. Goody, and Aymelt Itzen 9.1 Introduction 141 9.2 The Biological Problem 141 9.3 The Chemical Approach 143 9.4 Chemical Biological Research/Evaluation 150 9.5 Conclusions 152 References 153 10 Chemical Biology Approach to Suppression of Statin-Induced Muscle Toxicity 155 Bridget K.Wagner 10.1 Introduction 155 10.2 The Biological Problem 155 10.3 The Chemical Approach 157 10.4 Chemical Biology Research/Evaluation 158 10.5 Conclusion 161 References 162 11 A Target Identification System Based on MorphoBase, ChemProteoBase, and Photo-Cross-Linking Beads 163 Hiroyuki Osada, Makoto Muroi, Yasumitsu Kondoh, and Yushi Futamura 11.1 Introduction 163 11.2 The Biological Problem 163 11.3 Chemical Approaches 165 11.4 Chemical Biological Research/Evaluation 171 11.5 Conclusion 174 References 174 12 Activity-Based Proteasome Profiling in Medicinal Chemistry and Chemical Biology 177 Gerjan de Bruin, Nan Li, Guillem Paniagua, LianneWillems, Bo-Tao Xin, Martijn Verdoes, Paul Geurink,Wouter van der Linden, Mario van der Stelt, Gijs van der Marel, Herman Overkleeft, and Bogdan Florea 12.1 Introduction 177 12.2 The Biological Problem 177 12.3 The Chemical Approach 179 12.4 Biological Research/Evaluation 186 12.5 Conclusions 188 References 189 13 Rational Design of Activity-Based Retaining -Exoglucosidase Probes 191 Kah-Yee Li,Wouter Kallemeijn, Jianbing Jiang, MartheWalvoort, Lianne Willems, Thomas Beenakker, Hans van den Elst, Gijs van der Marel, Jeroen Codiee, Hans Aerts, Bogdan Florea, Rolf Boot, MartinWitte, and Herman Overkleeft 13.1 Introduction 191 13.2 The Biological Problem 191 13.3 The Chemical Approach 192 13.4 Biological Research/Evaluation 201 13.5 Conclusions 203 References 205 14 Modulation of ClpP Protease Activity: from Antibiotics to Antivirulence 207 Malte Gersch and Stephan A. Sieber 14.1 Introduction 207 14.2 The Biological Problem 207 14.3 The Chemical Approach 209 14.4 The Discovery of a Novel Antibiotic Mechanism 210 14.5 The Antivirulence Approach 215 14.6 Conclusions 219 References 219 15 Affinity-Based Isolation of Molecular Targets of Clinically Used Drugs 221 Shin-ichi Sato and Motonari Uesugi 15.1 Introduction The Biological/Medicinal Problem 221 15.2 The Chemical Approach 221 15.3 Chemical Biological Research 225 15.4 Conclusion 228 References 228 16 Identification of the Targets of Natural-Product-Inspired Mitotic Inhibitors 231 Kamal Kumar and Slava Ziegler 16.1 Introduction 231 16.2 The Biological Problem 231 16.3 The Chemical Approach 236 16.4 Chemical Biological Evaluation 239 16.5 Conclusion 246 References 247 17 Finding a Needle in a Haystack. Identification of Tankyrase, a Novel Therapeutic Target of the Wnt Pathway Using Chemical Genetics 249 Atwood K. Cheung and Feng Cong 17.1 Introduction 249 17.2 The Biological Problem 250 17.3 The Chemical Approach 251 17.4 Chemical Biological Research/Evaluation 254 17.5 Conclusion 260 References 261 18 The Identification of the Molecular Receptor of the Plant Hormone Abscisic Acid 265 Julian Oeljeklaus and Markus Kaiser 18.1 Introduction 265 18.2 The Biological Problem 267 18.3 The Chemical Genetics Approach 268 18.4 The Chemical Biology Approach 273 18.5 Conclusion 282 References 283 19 Chemical Biology in Plants: Finding New Connections between Pathways Using the Small Molecule Sortin1 285 Chunhua Zhang, Glenn R. Hicks, and Natasha V. Raikhel 19.1 Introduction 285 19.2 The Biological Problem 285 19.3 The Chemical Approach 286 19.4 Biological Research/Evaluation 292 19.5 Conclusion 293 Acknowledgment 293 References 294 20 Selective Targeting of Protein Interactions Mediated by BET Bromodomains 295 Susanne M uller, Hannah Lingard, and Stefan Knapp 20.1 Introduction 295 20.2 The Biological Problem 295 20.3 The Chemical Approach 298 20.4 Chemical/Biological Investigations 305 20.5 Conclusion 305 References 306 21 The Impact of Distant Polypharmacology in the Chemical Biology of PARPs 309 Albert A. Antolin and Jordi Mestres 21.1 Introduction 309 21.2 The Biological Problem 309 21.3 The Chemical Approach 312 21.4 Chemical Biological Research/Evaluation 315 21.5 Conclusions 319 References 320 22 Splicing Inhibitors: FromSmallMolecule to RNA Metabolism 323 Tilman Schneider-Poetsch and Minoru Yoshida 22.1 Introduction 323 22.2 The Biological Problem 323 22.3 The Chemical Approach 326 22.4 Chemical Biological Research/Evaluation 331 22.5 Conclusion 333 References 333 23 Photochemical Control of Gene Function in Zebrafish Embryos with Light-Activated Morpholinos 337 Qingyang Liu and Alexander Deiters 23.1 Introduction 337 23.2 The Biological Problem 337 23.3 The Chemical Approach 340 23.4 Chemical Biological Research/Evaluation 347 23.5 Conclusion 349 Acknowledgment 349 References 349 24 Life Cell Imaging of mRNA Using PNA FIT Probes 351 Andrea Knoll, Susann Kummer, Felix H ovelmann, Andreas Herrmann, and Oliver Seitz 24.1 Introduction 351 24.2 The Biological Problem 351 24.3 The Chemical Approach 352 24.4 Chemical Biological Research/Validation 355 24.5 Conclusion 361 References 362 25 Targeting the Transcriptional Hub -Catenin Using Stapled Peptides 365 Tom N. Grossmann and Gregory L. Verdine 25.1 Introduction 365 25.2 The Biological Problem 365 25.3 The Chemical Approach: Hydrocarbon Peptide Stapling 368 25.4 The Biological Approach: Phage-Display-Based Optimization 371 25.5 Biochemical and Biological Evaluation 375 25.6 Conclusions 376 References 377 26 Diversity-Oriented Synthesis: Developing New Chemical Tools to Probe and Modulate Biological Systems 379 Warren R. J. D. Galloway, David Wilcke, Feilin Nie, Kathy Hadje-Georgiou, Luca Laraia, and David R. Spring 26.1 Introduction 379 26.2 The Biological Problem 379 26.3 The Chemical Approach 382 26.4 Chemical Biology Research 384 26.5 Conclusion 388 References 388 27 Scaffold Diversity Synthesis with Branching Cascades Strategy 391 Kamal Kumar 27.1 Introduction 391 27.2 The Biological/Pharmacological Problem: Discovering Small Bioactive Molecules 391 27.3 The Chemical Approach: Scaffold Diversity 395 27.4 Chemical/Biological Evaluation Branching Cascades Strategy in Scaffold Diversity Synthesis 399 27.5 Conclusions 409 References 410 Index 415