Chemical Ligation

List of Figures xiii List of Plates xxiii List of Contributors xxix Preface xxxiii 1 Introduction to Chemical Ligation Reactions 1 Lucia De Rosa, Alessandra Romanelli, and Luca Domenico D’Andrea 1.1 Introduction 1 1.2 Chemical Ligation Chemistries 6 1.3 Imine Ligations 7 1.4 Serine/Threonine Ligation (STL) 21 1.5 Thioether Ligation 24 1.6 Thioester Ligation 25 1.7 ၖKetoacid–Hydroxylamine (KAHA) Ligation 49 1.8 Staudinger Ligation 52 1.9 Azide–Alkyne Cycloaddition 57 1.10 Diels–Alder Ligation 61 References 64 2 Protein Chemical Synthesis by SEA Ligation 89 Oleg Melnyk, Claire Simonneau, and Jérôme Vicogne 2.1 Introduction 89 2.2 Essential Chemical Properties of SEA Group 93 2.3 Protein Total Synthesis Using SEA Chemistry – SEAon/off Concept 97 2.4 Chemical Synthesis of HGF/SF Subdomains for Deciphering the Functioning of HGF/SF-MET System 106 2.5 Conclusion 114 References 114 3 Development of Serine/Threonine Ligation and Its Applications 125 Tianlu Li and Xuechen Li 3.1 Introduction 125 3.2 Serine/Threonine Ligation (STL) 130 3.3 Application of STL in Protein Synthesis 140 3.4 Conclusion and Outlook 154 References 154 4 Synthesis of Proteins by Native Chemical Ligation–Desulfurization Strategies 161 Bhavesh Premdjee and Richard J. Payne 4.1 Introduction 161 4.2 Ligation–Desulfurization and Early Applications 162 4.3 Beyond Native Chemical Ligation at Cysteine – The Development of Thiolated Amino Acids and Their Application in Protein Synthesis 174 4.4 Ligation–Deselenization in the Chemical Synthesis of Proteins 211 4.5 Conclusions and Future Directions 216 References 218 5 Synthesis of Chemokines by Chemical Ligation 223 Nydia Panitz and Annette G. Beck–Sickinger 5.1 Introduction – The Chemokine–Chemokine Receptor Multifunctional System 223 5.2 Synthesis of Chemokines by Native Chemical Ligation 224 5.3 Synthesis of Chemokines by Alternative Chemical Ligation 231 5.4 Semisynthesis of Chemokines by Expressed Protein Ligation 233 5.5 Prospects 241 References 243 6 Chemical Synthesis of Glycoproteins by the Thioester Method 251 Hironobu Hojo 6.1 Introduction 251 6.2 Ligation Methods and Strategy of Glycoprotein Synthesis 252 6.3 The Synthesis of the Extracellular Ig Domain of Emmprin 254 6.4 Synthesis of Basal Structure of MUC2 256 6.5 N–Alkylcysteine–Assisted Thioesterification Method and Dendrimer Synthesis 257 6.6 Synthesis of TIM–3 260 6.7 Resynthesis of Emmprin Ig Domain 262 6.8 Conclusion 264 References 264 7 Membrane Proteins: Chemical Synthesis and Ligation 269 Marc Dittman and Martin Engelhard 7.1 Introduction 269 7.2 Methods for the Synthesis and Purification of Membrane Proteins 270 7.3 Ligation and Refolding 273 7.4 Illustrative Examples 276 References 280 8 Chemoselective Modification of Proteins 285 Xi Chen, Stephanie Voss, and Yao-Wen Wu 8.1 Chemical Protein Synthesis 285 8.2 Chemoselective and Bioorthogonal Reactions 287 8.3 Site-Selective Protein Modification Approaches 307 References 322 9 Stable, Versatile Conjugation Chemistries for Modifying Aldehyde-Containing Biomolecules 339 Aaron E. Albers, Penelope M. Drake and David Rabuka 9.1 Introduction 339 9.2 Aldehyde as a Bioorthogonal Chemical Handle for Conjugation 339 9.3 Aldehyde Conjugation Chemistries 340 9.4 The Pictet–Spengler Ligation 341 9.5 The Hydrazinyl-Iso-Pictet–Spengler (HIPS) Ligation 341 9.6 The Trapped-Knoevenagel (thioPz) Ligation 343 9.7 Applications – Antibody–Drug Conjugates 346 9.8 Next-Generation HIPS Chemistry – AzaHIPS 348 9.9 Applications – Protein Engineering 349 9.10 Applications – Protein Labeling 349 9.11 Conclusions 351 References 351 10 Thioamide Labeling of Proteins through a Combination of Semisynthetic Methods 355 Christopher R. Walters, John J. Ferrie, and E. James Petersson 10.1 Introduction 355 10.2 Thioamide Synthesis 356 10.3 Thioamide Incorporation into Peptides 357 10.4 Synthesis of Full–Sized Proteins Containing Thioamides 360 10.5 Applications 368 10.6 Conclusions 381 Acknowledgments 381 References 382 11 Macrocyclic Organo-Peptide Hybrids by Intein-Mediated Ligation: Synthesis and Applications 391 John R. Frost and Rudi Fasan 11.1 Introduction 391 11.2 Macrocyclic Organo-Peptide Hybrids as Natural-Product-Inspired Macrocycles 396 11.3 Application of MOrPHs for Targeting α-Helix-Mediated Protein–Protein Interactions 406 11.4 Conclusions 410 References 410 12 Protein Ligation by HINT Domains 421 Hideo Iwaï and A. Sesilja Aranko 12.1 Introduction 421 12.2 Protein Ligation by Protein Splicing 423 12.3 Naturally Occurring and Artificially Split Inteins for Protein Ligation 424 12.4 Conditional Protein Splicing 427 12.5 Inter- and Intramolecular Protein Splicing 429 12.6 Protein Ligation by Other HINT Domains 430 12.7 Bottleneck of Protein Ligation by PTS 432 12.8 Comparison with Other Enzymatic Ligation Methods 432 12.9 Perspective of Protein Ligation by HINT Domains 437 12.10 Conclusions and Future Perspectives 438 Acknowledgment 438 References 438 13 Chemical Ligation for Molecular Imaging 447 Aurélien Godinat, Hacer Karatas, Ghyslain Budin, and Elena A. Dubikovskaya 13.1 Introduction 447 13.2 Chemical Ligation 448 13.3 Conclusion 470 References 473 14 Native Chemical Ligation in Structural Biology 485 Lucia De Rosa, Alessandra Romanelli, and Luca Domenico D’Andrea 14.1 Introduction 485 14.2 Protein (Semi)synthesis for Molecular Structure Determination 486 14.3 Protein (Semi)Synthesis for Understanding Protein Folding, Stability, and Interactions 494 14.4 Protein (Semi)Synthesis in Enzyme Chemistry 501 References 506 Index 517