Peptides: Chemistry and Biology

Автор(ы):Sewald N.
06.10.2007
Год изд.:2002
Описание: This book covers many different issues of peptide chemistry and biology, and is devoted to those students and scientists from many different disciplines who might seek quick reference to an essential point. In this way it provides the reader with concise, up-to-date information, as well as including many new references for those who wish to obtain a deeper insight into any particular issue. In this book, the "Virtual barrier" between peptides and proteins has been eliminated because, from the viewpoint of the synthesis or biological function of these compounds, such a barrier does not exist. This monograph represents a personal view of the authors on peptide chemistry and biology.
Оглавление:
Peptides: Chemistry and Biology — обложка книги.
1 Introduction and Background [1]
2 Fundamental Chemical and Structural Principles [5]
  2.1 Definitions and Main Conformational Features of the Peptide Bond [5]
  2.2 Building Blocks, Classification, and Nomenclature [7]
  2.3 Analysis of the Covalent Structure of Peptides and Proteins [11]
    2.3.1 Separation and Purification [12]
      2.3.1.1 Separation Principles [12]
      2.3.1.2 Purification Techniques [16]
      2.3.1.3 Stability Problems [18]
      2.3.1.4 Evaluation of Homogeneity [19]
    2.3.2 Primary Structure Determination [20]
      2.3.2.1 End Group Analysis [21]
      2.3.2.2 Cleavage of Disulfide Bonds [23]
      2.3.2.3 Analysis of Amino Acid Composition [24]
      2.3.2.4 Selective Methods of Cleaving Peptide Bonds [25]
      2.3.2.5 N-Terminal Sequence Analysis (Edman Degradation) [27]
      2.3.2.6 C-terminal Sequence Analysis [29]
      2.3.2.7 Mass Spectrometry [30]
      2.3.2.8 Peptide Ladder Sequencing [32]
      2.3.2.9 Assignment of Disulfide Bonds and Peptide Fragment Ordering [33]
      2.3.2.10 Location of Post-Translational Modifications and Bound Cofactors [35]
  2.4 Three-Dimensional Structure [36]
    2.4.1 Secondary Structure [36]
      2.4.1.1 Helix [37]
      2.4.1.2 p-Sheet [38]
      2.4.1.3 Turns [39]
      2.4.1.4 Amphiphilic Structures [41]
    2.4.2 Tertiary Structure [43]
      2.4.2.1 Structure Prediction [46]
  2.5 Methods of Structural Analysis [47]
    2.5.1 Circular Dichroism [48]
    2.5.2 Infrared Spectroscopy [49]
    2.5.3 NMR Spectroscopy [50]
    2.5.4 X-Ray Crystallography [52]
    2.5.5 UV Fluorescence Spectroscopy [54]
  2.6 References [55]
3 Biologically Active Peptides [61]
  3.1 Occurrence and Biological Roles [61]
  3.2 Biosynthesis [73]
    3.2.1 Ribosomal Synthesis [73]
    3.2.2 Post-translational Modification [76]
      3.2.2.1 Enzymatic Cleavage of Peptide Bonds [76]
      3.2.2.2 Hydroxylation [78]
      3.2.2.3 Carboxylation [78]
      3.2.2.4 Glycosylation [78]
      3.2.2.5 Amidation [83]
      3.2.2.6 Phosphorylation [83]
      3.2.2.7 Lipidation [85]
      3.2.2.8 Pyroglutamyl Formation [86]
      3.2.2.9 Sulfatation [87]
    3.2.3 Nonribosomal Synthesis [88]
  3.3 Selected Bioactive Peptide Families [90]
    3.3.1 Peptide and Protein Hormones [90]
      3.3.1.1 Liberins and Statins [92]
      3.3.1.2 Pituitary Hormones [96]
      3.3.1.3 Neurohypophyseal Hormones [98]
      3.3.1.4 Gastrointestinal Hormones [99]
      3.3.1.5 Pancreatic Islet Hormones [100]
      3.3.1.6 Further Physiologically Relevant Peptide Hormones [103]
    3.3.2 Neuropeptides [107]
      3.3.2.1 Opioid Peptides [109]
      3.3.2.2 Tachykinins [114]
      3.3.2.3 Further Selected Neuroactive Peptides [116]
    3.3.3 Peptide Antibiotics [119]
      3.3.3.1 Nonribosomally Synthesized Peptide Antibiotics [119]
      3.3.3.2 Ribosomally Synthesized Peptide Antibiotics [124]
    3.3.4 Peptide Toxins [126]
  3.4 References [130]
4 Peptide Synthesis [135]
  4.1 Principles and Objectives [135]
    4.1.1 Main Targets of Peptide Synthesis [135]
      4.1.1.1 Confirmation of Suggested Primary Structures [135]
      4.1.1.2 Design of Bioactive Peptide Drugs [136]
      4.1.1.3 Preparation of Pharmacologically Active Peptides and Proteins [137]
      4.1.1.4 Synthesis of Model Peptides [138]
    4.1.2 Basic Principles of Peptide Bond Formation [139]
  4.2 Protection of Functional Groups [142]
    4.2.1 Na-Amino Protection [143]
      4.2.1.1 Alkoxycarbonyl-Type (Urethane-Type) Protecting Groups [143]
      4.2.1.2 Carboxamide-Type Protecting Groups [152]
      4.2.1.3 Sulfonamide and Sulfenamide-Type Protecting Groups [152]
      4.2.1.4 Alkyl-Type Protecting Groups [153]
    4.2.2 Ca-Carboxy Protection [154]
      4.2.2.1 Esters [155]
      4.2.2.2 Amides and Hydrazides [157]
    4.2.3 C-terminal and Backbone Na-Carboxamide Protection [160]
    4.2.4 Side-chain Protection [162]
      4.2.4.1 Guanidino Protection [162]
      4.2.4.2 co-Amino Protection [165]
      4.2.4.3 co-Carboxy Protection [166]
      4.2.4.4 Thiol Protection [168]
      4.2.4.5 Imidazole Protection [171]
      4.2.4.6 Hydroxy Protection [174]
      4.2.4.7 Thioether Protection [176]
      4.2.4.8 Indole Protection [177]
      4.2.4.9 co-Amide Protection [178]
    4.2.5 Enzyme-labile Protecting Groups [180]
      4.2.5.1 Enzyme-labile Na-Amino Protection [181]
      4.2.5.2 Enzyme-labile Ca-Carboxy Protection and Enzyme-labile Linker Moieties [182]
    4.2.6 Protecting Group Compatibility [184]
  4.3 Peptide Bond Formation [184]
    4.3.1 Acyl Azides [185]
    4.3.2 Anhydrides [186]
      4.3.2.1 Mixed Anhydrides [187]
      4.3.2.2 Symmetrical Anhydrides [189]
      4.3.2.3 N-Carboxy Anhydrides [190]
    4.3.3 Carbodiimides [191]
    4.3.4 Active Esters [195]
    4.3.5 Acyl Halides [200]
    4.3.6 Phosphonium Reagents [201]
    4.3.7 Uronium Reagents [202]
    4.3.8 Further Special Methods [204]
  4.4 Racemization During Synthesis [205]
    4.4.1 Direct Enolization [205]
    4.4.2 5(4H)-Oxazolone Mechanism [205]
    4.4.3 Racemization Tests: Stereochemical Product Analysis [208]
  4.5 Solid-Phase Peptide Synthesis (SPPS) [209]
    4.5.1 Solid Supports and Linker Systems [212]
    4.5.2 Safety-Catch Linkers [220]
    4.5.3 Protection Schemes [224]
      4.5.3.1 Boc/Bzl-protecting Groups Scheme (Merrifield Tactics) [224]
      4.5.3.2 Fmoc/tBu-protecting Groups Scheme (Sheppard Tactics) [225]
      4.5.3.3 Three- and More-Dimensional Orthogonality [227]
    4.5.4 Chain Elongation [227]
      4.5.4.1 Coupling Methods [227]
      4.5.4.2 Undesired Problems During Elongation [228]
      4.5.4.3 Difficult Sequences [230]
      4.5.4.4 On-Resin Monitoring [232]
    4.5.5 Automation of the Process [232]
    4.5.6 Special Methods [233]
    4.5.7 Peptide Cleavage from the Resin [235]
      4.5.7.1 Acidolytic Methods [235]
      4.5.7.2 Side reactions [236]
      4.5.7.3 Advantages and Disadvantages of the Boc/Bzl and Fmoc/tBu Schemes [237]
    4.5.8 Examples of Syntheses by Linear SPPS [237]
  4.6 Biochemical Synthesis [238]
    4.6.1 Recombinant DNA Techniques [239]
      4.6.1.1 Principles of DNA Technology [239]
      4.6.1.2 Examples of Synthesis by Genetic Engineering [243]
      4.6.1.3 Cell-free Translation Systems [244]
    4.6.2 Enzymatic Peptide Synthesis [247]
      4.6.2.1 Introduction [247]
      4.6.2.2 Approaches to Enzymatic Synthesis [248]
      4.6.2.3 Manipulations to Suppress Competitive Reactions [250]
      4.6.2.4 Irreversible C-N Ligations by Mimicking Enzyme Specificity [251]
    4.6.3 Antibody-catalyzed Peptide Bond Formation [253]
  4.7 References [256]
5 Synthesis Concepts for Peptides and Proteins [269]
  5.1 Strategy and Tactics [269]
    5.1.1 Linear or Stepwise Synthesis [269]
    5.1.2 Segment Condensation or Convergent Synthesis [272]
    5.1.3 Tactical Considerations [273]
      5.1.3.1 Selected Protecting Group Schemes [273]
      5.1.3.2 Preferred Coupling Techniques [276]
  5.2 Synthesis in Solution [277]
    5.2.1 Convergent Synthesis of Maximally Protected Segments [277]
      5.2.1.1 The Sakakibara Approach to Protein Synthesis [278]
      5.2.1.2 Condensation of Lipophilic Segments [280]
    5.2.2 Convergent Synthesis of Minimally Protected Segments [282]
      5.2.2.1 Chemical Approaches [282]
      5.2.2.2 Enzymatic Approaches [284]
  5.3 Optimized Strategies on Polymeric Support [286]
    5.3.1 Stepwise SPPS [286]
    5.3.2 Convergent SPPS [288]
      5.3.2.1 Solid-phase Synthesis of Protected Segments [289]
      5.3.2.2 Solid Support-mediated Segment Condensation [290]
    5.3.3 Phase Change Synthesis [292]
    5.3.4 Soluble-Handle Approaches [293]
      5.3.4.1 Picolyl Ester Method [293]
      5.3.4.2 Liquid-Phase Method [293]
  5.4 Ligation of Unprotected Peptide Segments [294]
    5.4.1 Backbone-engineered Ligation [295]
    5.4.2 Prior Capture-mediated Ligation [297]
      5.4.2.1 Template-mediated Ligation [297]
      5.4.2.2 Native Chemical Ligation [298]
    5.4.3 Biochemical Protein Ligation [304]
  5.5 References [306]
6 Synthesis of Special Peptides and Peptide Conjugates [311]
  6.1 Cyclopeptides [311]
    6.1.1 Backbone Cyclization (Head-to-Tail Cyclization) [313]
    6.1.2 Side Chain-to-Head and Tail-to-Side Chain Cydizations [319]
    6.1.3 Side Chain-to-Side Chain Cyclizations [319]
  6.2 Cystine Peptides [320]
  6.3 Glycopeptides [322]
  6.4 Phosphopeptides [329]
  6.5 Lipopeptides [331]
  6.6 Sulfated Peptides [333]
  6.7 References [334]
7 Peptide and Protein Design, Pseudopeptides, and Peptidomimetics [339]
  7.1 Peptide Design [340]
  7.2 Modified Peptides [345]
    7.2.1 Side-Chain Modification [345]
    7.2.2 Baclcbone Modification [348]
    7.2.3 Combined Modification (Global Restriction) Approaches [350]
    7.2.4 Modification by Secondary Structure Mimetics [352]
    7.2.5 Transition State Inhibitors [353]
  7.3 Peptidomimetics [354]
  7.4 Pseudobiopolymers [357]
    7.4.1 Peptoids [358]
    7.4.2 Peptide Nucleic Acids (PNA) [360]
    7.4.3 (?)-Peptides, Hydrazino Peptides, Aminoxy Peptides, and Oligosulfonamides [361]
    7.4.4 Oligocarbamates [362]
    7.4.5 Oligopyrrolinones [363]
  7.5 Macropeptides and De-novo Design of Peptides and Proteins [364]
    7.5.1 Protein Design [364]
    7.5.2 Peptide Dendrimers [369]
    7.5.3 Peptide Polymers [371]
  7.6 References [372]
8 Combinatorial Peptide Synthesis [379]
  8.1 Parallel Synthesis [382]
    8.1.1 Synthesis in Teabags [383]
    8.1.2 Synthesis on Polyethylene Pins (Multipin Synthesis) [384]
    8.1.3 Parallel Synthesis of Single Compounds on Cellulose or Polymer Strips [385]
    8.1.4 Light-Directed, Spatially Addressable Parallel Synthesis [387]
    8.1.5 Liquid-Phase Synthesis using Soluble Polymeric Support [388]
  8.2 Synthesis of Mixtures [389]
    8.2.1 Reagent Mixture Method [389]
    8.2.2 Split and Combine Method [390]
    8.2.3 Encoding Methods [392]
    8.2.4 Peptide Library Deconvolution [396]
    8.2.5 Biological Methods for the Synthesis of Peptide Libraries [397]
  8.3 References [399]
9 Application of Peptides and Proteins [403]
  9.1 Protein Pharmaceuticals [403]
    9.1.1 Importance and Sources [403]
    9.1.2 Endogenous Pharmaceutical Proteins [404]
    9.1.3 Engineering of Therapeutic Proteins [406]
      9.1.3.1 Peptide-Based Vaccines [407]
      9.1.3.2 Monoclonal Antibodies [407]
      9.1.3.3 Protein Pharmaceuticals with Various Functions [409]
      9.1.3.4 Future Perspectives [410]
  9.2 Large-Scale Peptide Synthesis [412]
  9.3 Peptide Pharmaceuticals [416]
    9.3.1 Peptide Drugs and Drug Candidates [416]
    9.3.2 Peptide Drug Delivery Systems [419]
    9.3.3 Peptides as Tools in Drug Discovery [421]
      9.3.3.1 Peptides Targeted to Functional Sites of Proteins [422]
      9.3.3.2 Peptides Used in Target Validation [423]
      9.3.3.3 Peptides as Surrogate Ligands for HTS [424]
  9.4 References [425]
Glossary [429]
Index [545]
Формат: djvu
Размер:7108674 байт
Язык:RUS
Рейтинг: 241 Рейтинг
Открыть: