Amino Acids, Peptides and Proteins in Organic Chemistry, Volume 2, Modified Amino Acids, Organocatalysis and Enzymes

List of Contributors XIX

Part One Synthesis and Chemistry of Modified Amino Acids 1

1 Synthesis and Chemistry of a,b-Didehydroamino Acids 3
Uli Kazmaier

1.1 Introduction 3

1.2 Synthesis of DDAAs 3

1.3 Reactions of DDAAs 14

1.4 Conclusions 21

1.5 Experimental Procedures 22

2 Synthesis and Chemistry of a-Hydrazino Acids 35
Joëlle Vidal

2.1 Introduction 35

2.2 Synthesis 41

2.3 Chemistry 63

2.4 Conclusions 78

2.5 Experimental Procedures 79

3 Hydroxamic Acids: Chemistry, Bioactivity, and Solution and Solid-Phase Synthesis 93
Darren Griffith, Marc Devocelle, and Celine J. Marmion

3.1 Introduction 93

3.2 Chemistry, Bioactivity, and Clinical Utility 93

3.3 Solution-Phase Synthesis of Hydroxamic Acids 106

3.4 Solid-Phase Synthesis of Hydroxamic Acids 121

3.5 Conclusions 130

3.6 Experimental Procedures 130

References 137

4 Chemistry of a-Aminoboronic Acids and their Derivatives 145
Valery M. Dembitsky and Morris Srebnik

4.1 Introduction 145

4.2 Synthesis of a-Aminoboronic Acids 146

4.3 Synthesis of a-Amidoboronic Acid Derivatives 146

4.4 Asymmetric Synthesis via a-Haloalkylboronic Esters 151

4.5 Synthesis of Glycine a-Aminoboronic Acids 154

4.6 Synthesis of Proline a-Aminoboronic Acids 155

4.7 Synthesis of Alanine a-Aminoboronic Acids 162

4.8 Synthesis of Ornithine a-Aminoboronic Acids 164

4.9 Synthesis of Arginine a-Aminoboronic Acids 167

4.10 Synthesis of Phenethyl Peptide Boronic Acids 170

4.11 Synthesis via Zirconocene Species 172

4.12 Synthesis and Activity of Amine-Carboxyboranes and their Derivatives 174

4.13 Synthesis of Boron Analogs of Phosphonoacetates 179

4.14 Conclusions 183

References 183

5 Chemistry of Aminophosphonic Acids and Phosphonopeptides 189
Valery P. Kukhar and Vadim D. Romanenko

5.1 Introduction 189

5.2 Physical/Chemical Properties and Analysis 191

5.3 Synthesis of a-Aminophosphonic Acids 193

5.4 Synthesis of b-Aminophosphonates 212

5.5 Synthesis of g-Aminophosphonates and Higher Homologs 219

5.6 Phosphono- and Phosphinopeptides 227

5.7 Remarks on the Practical Utility of Aminophosphonates 240

5.8 Conclusions 245

5.9 Experimental Procedures 246

References 249

6 Chemistry of Silicon-Containing Amino Acids 261
Yingmei Qi and Scott McN. Sieburth

6.1 Introduction 261

6.2 Synthesis of Silicon-Containing Amino Acids 263

6.3 Reactions of Silicon-Containing Amino Acids 271

6.4 Bioactive Peptides Incorporating Silicon-Substituted Amino Acids 272

6.5 Conclusions 275

6.6 Experimental Procedures 276

References 278

Part Two Amino Acid Organocatalysis 281

7 Catalysis of Reactions by Amino Acids 283
Haibo Xie, Thomas Hayes, and Nicholas Gathergood

7.1 Introduction 283

7.2 Aldol Reaction 285

7.3 Mannich Reaction 298

7.4 a-Amination Reaction 306

7.5 Michael Reaction 308

7.6 Morita–Baylis–Hillman Reaction and Its Aza-Counterpart 319

7.7 Miscellaneous Amino Acid-Catalyzed Reactions 321

7.8 Sustainability of Amino Acid Catalysis 328

7.9 Conclusions and Expectations 330

7.10 Typical Procedures for Preferred Catalysis of Reactions by Amino Acids 330

References 333

Part Three Enzymes 339

8 Proteases as Powerful Catalysts for Organic Synthesis 341
Andrés Illanes, Fanny Guzmán, and Sonia Barberis

8.1 Enzyme Biocatalysis 341

8.2 Proteolytic Enzymes: Mechanisms and Characteristics 345

8.3 Proteases as Process Catalysts 348

8.4 Proteases in Organic Synthesis 350

8.5 Peptide Synthesis 350

8.6 Conclusions 360

References 361

9 Semisynthetic Enzymes 379
Usama M. Hegazy and Bengt Mannervik

9.1 Usefulness of Semisynthetic Enzymes 379

9.2 Natural Protein Biosynthesis 380

9.3 Sense Codon Reassignment 381

9.4 Missense Suppression 385

9.5 Evolving the Orthogonal aaRS/tRNA Pair 387

9.6 Nonsense Suppression 390

9.7 Mischarging of tRNA by Ribozyme 395

9.8 Evolving the Orthogonal Ribosome/mRNA Pair 396

9.9 Frame-Shift Suppression 397

9.10 Noncanonical Base Pairs 399

9.11 Chemical Ligation 401

9.12 Inteins 404

9.13 EPL 410

9.14 Post-Translational Chemical Modification 411

9.15 Examples of Semisynthetic Enzymes 415

9.16 Conclusions 419

References 419

10 Catalysis by Peptide-Based Enzyme Models 433
Giovanna Ghirlanda, Leonard J. Prins, and Paolo Scrimin

10.1 Introduction 433

10.2 Peptide Models of Hydrolytic Enzymes 434

10.3 Peptide Models of Heme Proteins 456

10.4 Conclusions 467

References 467

11 Substrate Recognition 473
Keith Brocklehurst, Sheraz Gul, and Richard W. Pickersgill

11.1 Recognition, Specificity, Catalysis, Inhibition, and Linguistics 473

11.2 Serine Proteinases 476

11.3 Cysteine Proteinases 480

11.4 Glycoside Hydrolases 485

11.5 Protein Kinases 488

11.6 aaRSs 490

11.7 Lipases 492

11.8 Conclusions 493

References 494

12 Protein Recognition 505
Robyn E. Mansfield, Arwen J. Cross, Jacqueline M. Matthews, and Joel P. Mackay

12.1 General Introduction 505

12.2 Nature of Protein Interfaces 506

12.3 Affinity of Protein Interactions 509

12.4 Measuring Protein Interactions 512

12.5 Coupled Folding and Binding 515

12.6 Regulation of Interactions by PTMs 519

12.7 Engineering and Inhibiting Protein–Protein Interactions 521

12.8 Conclusions 527

References 527

13 Mammalian Peptide Hormones: Biosynthesis and Inhibition 533
Karen Brand and Annette G. Beck-Sickinger

13.1 Introduction 533

13.2 Mammalian Peptide Hormones 534

13.3 Biosynthesis of Peptide Hormones 535

13.4 Inhibition of Biosynthesis 555

13.5 Conclusions 565

References 565

14 Insect Peptide Hormones 575
R. Elwyn Isaac and Neil Audsley

14.1 Introduction 575

14.2 Structure and Biosynthesis of Insect Peptide Hormones 576

14.3 Proctolin 578

14.4 Sex Peptide 580

14.5 A-Type Allatostatins 582

14.6 CRF-Related Diuretic Hormones (DH) 584

14.7 Insect Peptide Hormones and Insect Control 586

14.8 Conclusions 589

References 590

15 Plant Peptide Signals 597
Javier Narváez-Vásquez, Martha L. Orozco-Cárdenas, and Gregory Pearce

15.1 Introduction 597

15.2 Defense-Related Peptides 599

15.3 Peptides Involved in Growth and Development 605

15.4 Peptides Involved in Self-Recognition 615

15.5 Methods in Plant Regulatory Peptide Research 616

15.6 Conclusions 623

References 624

16 Nonribosomal Peptide Synthesis 631
Sean Doyle

16.1 Introduction 631

16.2 NRPs 632

16.3 NRP Synthetase Domains 635

16.4 PPTases 639

16.5 Experimental Strategies for NRPS Investigations 642

16.6 Non-NRPS 649

16.7 Conclusions 650

References 650

Index 657