Concepts and Case Studies in Chemical Biology

  • ID: 2755170
  • Book
  • 464 Pages
  • John Wiley and Sons Ltd
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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.

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List of Contributors XVII

Introduction and Preface XXV

Abbreviations XXIX

1 Real–Time and Continuous Sensors of Protein Kinase Activity Utilizing Chelation–Enhanced Fluorescence 1Laura 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 17Daniel 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 37Birgit Hoeger and Maja Köhn

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 51YansongWang and Maja Köhn

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 63Gemma 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 83Yaowen 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 105Gemma 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 123Frank 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 141Christian 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 155Bridget 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 163Hiroyuki 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 177Gerjan 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 191Kah–Yee Li,Wouter Kallemeijn, Jianbing Jiang, MartheWalvoort, Lianne Willems, Thomas Beenakker, Hans van den Elst, Gijs van der Marel, Jeroen Codìee, 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 207Malte 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 221Shin–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 231Kamal 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 249Atwood 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 265Julian 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 285Chunhua 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 295Susanne 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 309Albert A. Antolín 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 323Tilman 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 337Qingyang 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 351Andrea 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 365Tom 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 379Warren 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 391Kamal 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

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Herbert Waldmann
Petra Janning
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