Chapter
Chapter 1 Introduction to Chemical Ligation Reactions
1.1.1 Chemical Synthesis of Proteins: From the Stepwise Synthesis to the Chemical Ligation Approach
1.1.2 Chemical Modification of Proteins: From Conventional Methods to Chemoselective Labeling by Chemical Ligation
1.2 Chemical Ligation Chemistries
1.3.3 Pictet–Spengler Ligation
1.3.4 Thiazolidine Ligation
1.4 Serine/Threonine Ligation (STL)
1.6.1 Native Chemical Ligation (NCL)
1.6.2 Expressed Protein Ligation (EPL)
1.6.3 Thioacid-Mediated Ligation Strategies
1.7 α-Ketoacid-Hydroxylamine (KAHA) Ligation
1.7.1 Acyltrifluoroborates and Hydroxylamines Ligation
1.9 Azide–Alkyne Cycloaddition
1.10 Diels–Alder Ligation
Chapter 2 Protein Chemical Synthesis by SEA Ligation
2.2 Essential Chemical Properties of SEA Group
2.3 Protein Total Synthesis Using SEA Chemistry – SEAon/off Concept
2.3.1 Synthesis of SEAoff Peptide Segments
2.3.2 SEAon/off Concept and the Design of a One-Pot Three Peptide Segment Assembly Process
2.3.3 SEA on/off Concept and the Solid-Phase Synthesis of Proteins in the N-to-C Direction
2.4 Chemical Synthesis of HGF/SF Subdomains for Deciphering the Functioning of HGF/SF-MET System
Chapter 3 Development of Serine/Threonine Ligation and Its Applications
3.1.1 Protein Synthesis by SPPS
3.1.2 Native Chemical Ligation (and Extended Desulfurization)
3.2 Serine/Threonine Ligation (STL)
3.2.1 SAL Ester Preparation
3.2.2 N-Terminal-Protecting Group for Successive C-to-N Ser/Thr Ligations
3.2.3 Scope and Limitations
3.3 Application of STL in Protein Synthesis
3.3.1 Consecutive STL of Peptides/Proteins
3.3.2 STL-Mediated Peptide Cyclization
3.3.3 Thiol SAL Ester-Mediated Aminolysis in Peptide Cyclization
3.3.4 A Fluorogenic Probe for Recognizing 5-OH-Lys Inspired by STL
3.3.5 Expressed Protein Semisynthesis via Ser/Thr Ligation
3.4 Conclusion and Outlook
Chapter 4 Synthesis of Proteins by Native Chemical Ligation–Desulfurization Strategies
4.2 Ligation–Desulfurization and Early Applications
4.2.1 Metal‐Free Desulfurization
4.2.2 Ligation–Desulfurization toward the Synthesis of Proteins
4.3 Beyond Native Chemical Ligation at Cysteine – The Development of Thiolated Amino Acids and Their Application in Protein Synthesis
4.4 Ligation–Deselenization in the Chemical Synthesis of Proteins
4.4.1 Selenol Amino Acids
4.5 Conclusions and Future Directions
Chapter 5 Synthesis of Chemokines by Chemical Ligation
5.1 Introduction – The Chemokine–Chemokine Receptor Multifunctional System
5.2 Synthesis of Chemokines by Native Chemical Ligation
5.3 Synthesis of Chemokines by Alternative Chemical Ligation
5.4 Semisynthesis of Chemokines by Expressed Protein Ligation
Chapter 6 Chemical Synthesis of Glycoproteins by the Thioester Method
6.2 Ligation Methods and Strategy of Glycoprotein Synthesis
6.3 The Synthesis of the Extracellular Ig Domain of Emmprin
6.4 Synthesis of Basal Structure of MUC2
6.5 N-Alkylcysteine-Assisted Thioesterification Method and Dendrimer Synthesis
6.7 Resynthesis of Emmprin Ig Domain
Chapter 7 Membrane Proteins: Chemical Synthesis and Ligation
7.2 Methods for the Synthesis and Purification of Membrane Proteins
7.2.1 Synthesis of Hydrophobic Peptides
7.2.2 Purification of Hydrophobic Peptides
7.3 Ligation and Refolding
7.3.1 Ligation Strategies
7.3.2 Refolding of Chemically Synthesized Hydrophobic Peptides and Membrane Proteins
7.4 Illustrative Examples
7.4.1 Diacylglycerol Kinase (DAGK)
7.4.2 Semisynthesis of the Sensory Rhodopsin/Transducer Complex
7.4.3 Semisynthesis of the Functional K+ Channel KcsA
Chapter 8 Chemoselective Modification of Proteins
8.1 Chemical Protein Synthesis
8.1.1 Native Chemical Ligation (NCL) and Expressed Protein Ligation (EPL)
8.1.2 Traceless Staudinger Ligation
8.2 Chemoselective and Bioorthogonal Reactions
8.2.1 Oxime/Hydrazone Ligation
8.2.2 Staudinger Ligations
8.2.3 Copper-Catalyzed Azide–Alkyne Cycloaddition (CuAAC)
8.2.4 Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC)
8.2.5 Inverse Electron-Demand Diels–Alder Cycloaddition (DAINV)
8.2.6 Light-Induced Click Reactions
8.2.7 1,2-Aminothiol Condensation
8.2.8 Transition-Metal-Catalyzed Couplings
8.2.9 Miscellaneous Protein-Labeling Reactions
8.3 Site-Selective Protein Modification Approaches
8.3.1 Site-Selective Modification of Native Proteins
8.3.2 Chemical Tags for Labeling Proteins in Live Cells
8.3.3 Unnatural Amino Acid Mutagenesis
Chapter 9 Stable, Versatile Conjugation Chemistries for Modifying Aldehyde-Containing Biomolecules
9.2 Aldehyde as a Bioorthogonal Chemical Handle for Conjugation
9.3 Aldehyde Conjugation Chemistries
9.4 The Pictet–Spengler Ligation
9.5 The Hydrazinyl-Iso-Pictet–Spengler (HIPS) Ligation
9.6 The Trapped-Knoevenagel (thioPz) Ligation
9.7 Applications – Antibody–Drug Conjugates
9.8 Next-Generation HIPS Chemistry – AzaHIPS
9.9 Applications – Protein Engineering
9.10 Applications – Protein Labeling
Chapter 10 Thioamide Labeling of Proteins through a Combination of Semisynthetic Methods
10.3 Thioamide Incorporation into Peptides
10.4 Synthesis of Full-Sized Proteins Containing Thioamides
10.5.1 Structural Studies
10.5.2 Use as Photoswitches
10.5.3 Site-Specific Circular Dichroism Labels
10.5.4 Fluorescence Quenching
10.5.5 Protein Folding in Model Systems
10.5.6 Monitoring Proteolysis
10.5.7 α-Synuclein Misfolding Studies
Chapter 11 Macrocyclic Organo-Peptide Hybrids by Intein-Mediated Ligation: Synthesis and Applications
11.1.1 Naturally Occurring Macrocyclic Peptides
11.1.2 Natural Product Analogs via Reengineering of NRPS and PRPS Biosynthetic Pathways
11.2 Macrocyclic Organo-Peptide Hybrids as Natural-Product-Inspired Macrocycles
11.2.1 MOrPHs via CuAAC/Hydrazide-Mediated Ligation
11.2.2 Catalyst-Free MOrPH Synthesis via Oxime/AMA-Mediated Ligation
11.2.3 Structure–Reactivity Relationships in MOrPH Synthesis
11.2.4 Synthesis of MOrPH Libraries
11.2.5 Macrocyclization Mech
11.2.6 Bicyclic Organo-Peptide Hybrids
11.3 Application of MOrPHs for Targeting α-Helix-Mediated Protein–Protein Interactions
Chapter 12 Protein Ligation by HINT Domains
12.2 Protein Ligation by Protein Splicing
12.3 Naturally Occurring and Artificially Split Inteins for Protein Ligation
12.4 Conditional Protein Splicing
12.5 Inter- and Intramolecular Protein Splicing
12.6 Protein Ligation by Other HINT Domains
12.7 Bottleneck of Protein Ligation by PTS
12.8 Comparison with Other Enzymatic Ligation Methods
12.9 Perspective of Protein Ligation by HINT Domains
12.10 Conclusions and Future Perspectives
Chapter 13 Chemical Ligation for Molecular Imaging
13.2.1 Classical Chemical Ligation
13.2.2 Bioorthogonal Chemistry
Chapter 14 Native Chemical Ligation in Structural Biology
14.2 Protein (Semi)synthesis for Molecular Structure Determination
14.3 Protein (Semi)Synthesis for Understanding Protein Folding, Stability, and Interactions
14.4 Protein (Semi)Synthesis in Enzyme Chemistry
Chemical Ligation
：Tools for Biomolecule Synthesis and Modification
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