| | Table of Contents | |
| | | |
| |
| | Preface | IX |
| | List of Authors | XI |
| 1 | Artificial Enzymes
Ronald Breslow | 1 |
| 1.1 | Mimics of Enzymes that use Thiamine Pyrophosphate as a Coenzyme | 1 |
| 1.2 | Mimics of Enzymes that use Pyridoxamine and Pyridoxal Phosphates as Coenzymes | 3 |
| 1.3 | Artificial Hydrolytic Enzymes | 3 |
| 1.3.1 | Chymotrypsin Mimics | 3 |
| 1.3.2 | Metalloenzyme Mimics | 5 |
| 1.3.3 | Artificial Ribonucleases | 9 |
| 1.3.4 | Artificial Enolases and Aldolases | 12 |
| 1.4 | Cytochrome P-450 Mimics | 15 |
| 1.4.1 | Aromatic Substitution in Cyclodextrin Complexes | 15 |
| 1.4.2 | Selective Photochemical Reactions | 17 |
| 1.4.3 | Directed Halogenations | 19 |
| 1.4.4 | Nitrene Insertions | 24 |
| 1.4.5 | Binding by Cyclodextrin Dimers | 25 |
| 1.4.6 | Hydroxylations by Artificial P-450 Enzymes | 27 |
| 1.5 | Future Prospects | 31 |
| 2 | Vitamin B6 Enzyme Models
Lei Liu and Ronald Breslow | 37 |
| 2.1 | Introduction | 37 |
| 2.2 | Transamination | 39 |
| 2.2.1 | Pyridoxamines with Small Auxiliary Groups | 39 |
| 2.2.3 | Pyridoxamine–Surfactant Systems | 46 |
| 2.2.4 | Vitamin B6–Polypeptide Systems | 48 |
| 2.2.5 | Polymeric and Dendrimeric Vitamin B6 Mimics | 50 |
| 2.3 | Racemization | 52 |
| 2.4 | Decarboxylation | 55 |
| 2.6 | Aldolase-type Reactions | 58 |
| 3 | Evolution of Synthetic Polymers with Enzyme-like Catalytic Activities
Irving M. Klotz and Junghun Suh | 63 |
| 3.1 | Introduction: Conceptual Background | 63 |
| 3.2 | Homogeneous Polymer Biocatalysts | 64 |
| 3.2.1 | Fabrication of Macromolecules with Strong Affinities for Ligands | 64 |
| 3.2.2 | Enhanced Reactivity of Nucleophiles in Polyethylenimines (PEIs) | 66 |
| 3.2.3 | Polyethylenimines with Nucleophile Adducts | 67 |
| 3.2.4 | Proximal Group Adducts to Polyethylenimines | 70 |
| 3.2.5 | Polyethylenimines (PEIs) with Adducts that Self-assemble into Catalytic Moieties | 74 |
| 3.3 | Heterogeneous Polymer Biocatalysts | 76 |
| 3.3.1 | Random Catalytic Adducts | 76 |
| 3.3.2 | Proximal Group Adducts | 78 |
| 3.3.3 | Adducts Containing Catalytic Modules Synthesized Priorto Incorporation into Polymers | 82 |
| 3.3.4 | Adducts giving Nuclease Activity to Polymers | 85 |
| 3.4 | Prospectives | 87 |
| 4 | Mimicking Enzymes with Antibodies
Donald Hilvert | 89 |
| 4.1 | Introduction | 89 |
| 4.2 | Basic Strategy | 90 |
| 4.3 | Evolution of Binding Affinity and Catalytic Efficiency | 91 |
| 4.4 | Importance of a Good Fit | 92 |
| 4.5 | General Acid–General Base Catalysis | 95 |
| 4.6 | Covalent Catalysis | 97 |
| 4.7 | Practical Applications | 100 |
| 4.8 | Future Directions | 103 |
| 4.9 | Outlook | 104 |
| 5 | Protein-based Artificial Enzymes
Ben Duckworth and Mark D. Distefano | 109 |
| 5.1 | Introduction | 109 |
| 5.2 | Artificial Nucleases Based on DNA and RNA Binding Proteins | 110 |
| 5.2.1 | Introduction | 110 |
| 5.2.2 | Artificial Nucleases from Native Protein Scaffolds | 110 |
| 5.2.3 | OP Nuclease Design by Mutagenesis and Chemical Modification | 112 |
| 5.2.4 | Additional Applications for OP Conjugates | 113 |
| 5.2.5 | A Fe-EDTA Artificial Nuclease | 114 |
| 5.2.6 | Concluding Remarks | 114 |
| 5.3 | Catalysts Based on Hollow Lipid-binding Proteins | 115 |
| 5.3.1 | Lipid-binding Proteins | 115 |
| 5.3.2 | Initial Work | 115 |
| 5.3.3 | Exploiting the Advantage of a Protein-based Scaffold | 116 |
| 5.3.4 | Catalytic Turnover with Rate Acceleration | 117 |
| 5.3.5 | Modulation of Cofactor Reactivity with Metal Ions | 119 |
| 5.3.6 | Chemogenetic Approach | 119 |
| 5.3.7 | Adding Functional Groups within the Cavity | 120 |
| 5.3.8 | Scaffold Redesign | 123 |
| 5.3.9 | Hydrolytic Reactions | 124 |
| 5.3.10 | A Flavin-containing Conjugate | 125 |
| 5.3.11 | Some Limitations | 125 |
| 5.4 | Myoglobin as a Starting Point for Oxidase Design | 126 |
| 5.4.1 | Artificial Metalloproteins and Myoglobin | 126 |
| 5.4.2 | Non-covalent Attachment of a Redox Center | 126 |
| 5.4.3 | Dual Anchoring Strategy | 127 |
| 5.5 | Antibodies as Scaffolds for Catalyst Design | 128 |
| 5.5.1 | Antibodies as Specificity Elements | 128 |
| 5.5.2 | Incorporation of an Imidazole Functional Group into an Antibody for Catalysis | 129 |
| 5.5.3 | Comparison of Imidazole-containing Antibodies Produced by Chemical Modification and Site-directed Mutagenesis | 129 |
| 5.6 | Conclusions | 130 |
| 6 | Artificial Hydrolytic Metalloenzymes
Jik Chin and Hae-Jo Kim | 133 |
| 6.1 | Introduction | 133 |
| 6.2 | Reactivity of Substrates | 133 |
| 6.3 | Lewis Acid Activation | 134 |
| 6.4 | Nucleophile Activation | 140 |
| 6.5 | Leaving-group Activation | 141 |
| 6.6 | Combining Lewis Acid Activation and Nucleophile Activation | 142 |
| 6.7 | Double Lewis Acid Activation | 144 |
| 6.8 | Phosphatase Models | 146 |
| 6.9 | Phosphodiesterase Models | 149 |
| 6.10 | Polymerases and DNases | 151 |
| 6.11 | Conclusion | 153 |
| 7 | Artificial Restriction Enzymes As Tools For Future Molecular Biology and Biotechnology
Yoji Yamamoto and Makoto Komiyama | 159 |
| 7.1 | Introduction | 159 |
| 7.2 | Significance of Artificial Restriction Enzymes | 159 |
| 7.3 | Non-enzymatic Catalysts for DNA Hydrolysis | 160 |
| 7.4 | Molecular Design of Artificial Restriction Enzymes (Covalent vs. Non-Covalent Strategy) | 161 |
| 7.4.1 | Covalent Strategy for the First-generation of Artificial Restriction Enzymes | 161 |
| 7.4.2 | Non-covalent Strategy for the Second-generation of Artificial Restriction Enzymes | 162 |
| 7.4.3 | Chemical Basis for “Non-covalent“ Strategy | 162 |
| 7.5 | Site-selective Scission of Single-stranded DNA | 163 |
| 7.5.1 | Promotion of Gap-selective DNA Hydrolysis by Introducing Monophosphate Groups to the Gap-site | 163 |
| 7.5.2 | Enzymatic Ligation of the Fragments Obtained by Site-selective Scission | 167 |
| 7.6 | Site-selective Scission of Double-stranded DNA by Combining Ce(IV)/EDTA Complex with Pseudo-complementary PNA | 169 |
| 7.6.1 | Design of Artificial Restriction Enzymes for Double-stranded DNA Scission | 169 |
| 7.6.2 | Site-selective Hydrolysis of Double-stranded DNA | 170 |
| 7.6.3 | Enzymatic Ligation of the Scission Fragment and Foreign DNA | 173 |
| 7.7 | Conclusion | 174 |
| | Index | 177 |
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