Amino Acids, Peptides And Proteins In Organic Chemistry - Building Blocks, Catalysis And Coupling Chemsitry V 3

Closing a gap in the literature, this is the only book series in 6 volumes to cover this important topic in organic and biochemistry. Drawing upon the combined expertise of the international "who's who" in amino acid research, this series is a real benchmark for amino acid chemistry, providing a comprehensive discussion of the occurrence, uses and applications of amino acids and, by extension, their polymeric forms, peptides and proteins. The practical value of each volume is heightened by the inclusion of experimental procedures.

This third volume in the series presents an in depth account of recent developments in the (bio-)synthesis of amino acids and peptides. Divided into two parts, the first section deals with amino acids as building blocks, including the generation of alpha-amino acids, beta-lactams, and heterocycles. The second section is devoted to the synthesis of peptides, with the focus on solid phase synthesis. However, solution phase peptide synthesis is covered as well, as are topics such as coupling reagents, chemical ligation, peptide purification and automation.

Andrew Hughes is a reader and associate professor of chemistry at La Trobe University, Melbourne, Australia. He obtained his degrees from the University of Western Australia, before taking up post-doctoral appointments at the University of Cambridge starting in 1989. After three years working with Professor Andrew Holmes, he joined Professor Steven Ley`s group. While at Cambridge he was appointed the Shell Research Fellow at Robinson College. His interests lie in the general field of asymmetric synthesis and methodology, with a recent focus on amino acid chemistry and difficult peptides.

List of Contributors.

Part One Amino Acids as Building Blocks.

1 Amino Acid Biosynthesis (Emily J. Parker and Andrew J. Pratt).

1.1 Introduction.

1.2 Glutamate and Glutamine: Gateways to Amino Acid Biosynthesis.

1.3 Other Amino Acids from Ubiquitous Metabolites: Pyridoxal Phosphate-Dependent Routes to Aspartate, Alanine, and Glycine.

1.4 Routes to Functionalized Three-Carbon Amino Acids: Serine, Cysteine, and Selenocysteine.

1.5 Other Amino Acids from Aspartate and Glutamate: Asparagine and Side Chain Functional Group Manipulation.

1.6 Aspartate and Glutamate Families of Amino Acids

1.7 Biosynthesis of Aliphatic Amino Acids with Modified Carbon Skeletons: Branched-Chain Amino Acids, Lysine, and Pyrrolysine.

1.8 Biosynthesis of the Aromatic Amino Acids.

1.9 Conclusions.

References.

2 Heterocycles from Amino Acids (M. Isabel Calaza and Carlos Cativiela).

2.1 Introduction.

2.2 Heterocycles Generated by Intramolecular Cyclizations.

2.3 Heterocycles Generated by Intermolecular Cyclizations.

2.4 Heterocycles Generated by Cycloadditions.

2.5 Conclusions.

2.6 Experimental Procedures.

3 Radical-Mediated Synthesis of α-Amino Acids and Peptides (Jan Deska).

3.1 Introduction.

3.2 Free Radical Reactions.

3.3 Radical Addition to Imine Derivatives.

3.4 Radical Conjugate Addition.

3.5 Conclusions.

3.6 Experimental Protocols.

4 Synthesis of β-Lactams (Cephalosporins) by Bioconversion (José Luis Barredo, Marta Rodriguez- Sáiz, José Luis Adrio, and Arnold L. Demain).

4.1 Introduction.

4.2 Biosynthetic Pathways of Cephalosporins and Penicillins.

4.3 Production of 7-ACA by A. chrysogenum.

4.4 Production of 7-ADCA by A. chrysogenum.

4.5 Production of Penicillin G by A. chrysogenum.

4.6 Production of Cephalosporins by P. chrysogenum.

4.7 Conversion of Penicillin G and other Penicillins to DAOG by Streptomyces clavuligerus.

4.8 Conclusions.

References.

5 Structure and Reactivity of β-Lactams (Michael I. Page).

5.1 Introduction.

5.2 Structure.

5.3 Reactivity.

5.4 Hydrolysis.

5.5 Aminolysis.

5.6 Epimerization.

References.

Part Two Amino Acid Coupling Chemistry.

6 Solution-Phase Peptide Synthesis (Yuko Tsuda and Yoshio Okada).

6.1 Principle of Peptide Synthesis.

6.2 Protection Procedures.

6.3 Chain Elongation Procedures. 

6.4 Final Deprotection Methods.

References.

7 Solid-Phase Peptide Synthesis: Historical Aspects (Garland R. Marshall).

7.1 Introduction.

7.2 Selection of Compatible Synthetic Components.

7.3 Racemization and Stepwise Peptide Assembly.

7.4 Optimization of Synthetic Components.

7.5 Foreshadowing of the Nobel Prize.

7.6 Automation of SPPS.

7.7 Impact of New Protecting Groups and Resin Linkages.

7.8 Solid-Phase Organic Chemistry.

7.9 Early Applications of SPPS to Small Proteins.

7.10 Side-Reactions and Sequence-Dependent Problems.

7.11 Rapid Expansion of Usage Leading to the Nobel Prize.

7.12 From the Nobel Prize Forward to Combinatorial Chemistry.

7.13 Protein Synthesis and Peptide Ligation.

7.14 Conclusions.

References.

8 Linkers for Solid-Phase Peptide Synthesis (Miroslav Soural, Jan Hlavá4c, and Viktor Krch4nák).

8.1 Introduction.

8.2 Immobilization via Carboxyl Group.

8.3 Immobilization via Amino Group.

8.4 Backbone Immobilization.

8.5 Immobilization via Amino Acid Side-Chain.

8.6 Conclusions.

References.

9 Orthogonal Protecting Groups and Side-Reactions in Fmoc/tBu Solid-Phase Peptide Synthesis (Stefano Carganico and Anna Maria Papini).

9.1 Orthogonal Protecting Groups in Fmoc/tBu Solid-Phase Peptide Synthesis.

9.2 Side-Reactions in Fmoc/tBu Solid-Phase Peptide Synthesis.

10 Fmoc Methodology: Cleavage from the Resin and Final Deprotection (Fernando Albericio, Judit Tulla-Puche, and Steven A. Kates).

10.1 Introduction.

10.2 ‘‘Low’’ TFA-Labile Resins.

10.3 ‘‘High’’ TFA-Labile Resins.

10.4 Final Remarks.

References.

11 Strategy in Solid-Phase Peptide Synthesis (Kleomenis Barlos and Knut Adermann).

11.1 Synthetic Strategies Utilizing Solid-Phase Peptide Synthesis Methods.

11.2 Solid Support: Resins and Linkers.

11.3 Developing the Synthetic Strategy: Selection of the Protecting Group Scheme.

11.4 Resin Loading.

11.5 SBS Peptide Chain Elongation: Coupling and Activation.

11.6 Piperazine Formation.

11.7 Solid-Phase Synthesis of Protected Peptide Segments.

11.8 Fragment Condensation Approach: Convergent and Hybrid Syntheses.

11.9 Cleavage from the Resin and Global Peptide Deprotection.

11.10 Disulfide Bond-Containing Peptides.

11.11 Native Chemical Ligation (NCL).

11.12 SPPS of Peptides Modified at their C-Terminus.

11.13 Side-Chain-Modified Peptides.

11.14 Cyclic Peptides.

11.15 Large-Scale Solid-Phase Synthesis.

11.16 Conclusions.

References.

12 Peptide-Coupling Reagents (Ayman El- Faham and Fernando Albericio)

12.1 Introduction.

12.2 Carbodiimides.

12.3 Phosphonium Salts.

12.4 Aminium/Uronium Salts.

12.5 Fluoroformamidinium Coupling Reagents.

12.6 Organophosphorus Reagents.

12.7 Triazine Coupling Reagents.

12.8 Mukaiyama.s Reagent.

12.9 Conclusions.

References.

13 Chemoselective Peptide Ligation: A Privileged Tool for Protein Synthesis (Christian P.R. Hackenberger, Jeffrey W. Bode, and Dirk Schwarzer).

13.1 Introduction.

13.2 Chemoselective Peptide Ligations Following a Capture/Rearrangement Strategy.

13.3 Chemical Transformations for Cys-Free Ligations in Peptides and Proteins.

13.4 Other Chemoselective Capture Strategies.

13.5 Peptide Ligations by Chemoselective Amide-Bond-Forming Reactions. 

13.6 Strategies for the Ligation of Multiple Fragments.

14 Automation of Peptide Synthesis (Carlo Di Bello, Andrea Bagno, and Monica Dettin).

14.1 Introduction.

14.2 SPPS: From Mechanization to Automation.

14.3 Deprotection Step: Monitoring and Control.

14.4 Coupling Step: Monitoring and Control.

14.5 Integrated Deprotection and Coupling Control.

References.

15 Peptide Purification by Reversed-Phase Chromatography (Ulrike Kusebauch, Joshua McBee, Julie Bletz, Richard J. Simpson, and Robert L. Moritz).

15.1 RP-HPLC of Peptides.

15.2 Peptide properties.

15.3 Chromatographic Principles.

15.4 Prediction of Peptide Retention Times.

15.5 Advantages of Reduced Scale.

15.6 Two-Dimensional Chromatographic Methods.

15.7 Peptide Analysis in Complex Biological Matrices.

15.8 Standard Methods for Peptide Separations for Analysis by Hyphenated Techniques.

15.9 Emerging Methods for Peptide Separations for Analysis by Hyphenated Techniques.

15.10 Practical use of RP-HPLC for Purifying Peptides (Analytical and Preparative Scale).

16 Difficult Peptides (M. Terêsa Machini Miranda, Cleber W. Liria, and Cesar Remuzgo).

16.1 Importance of Peptide Synthesis.

16.2 Methods for Peptide Synthesis.

16.3 Chemical Peptide Synthesis.

16.4 ‘‘Difficult Peptide Sequences’’.

16.5 Means to Overcome Peptide Aggregation in SPPS.

16.6 Monitoring the Synthesis of a ‘‘Difficult Peptide’’.

16.7 Conclusions.

References.

Index.