基本説明
Topics: Theoretical aspects of structure, mechanism and kinetics; practical considerations, from immunization techniques to screening methods; in vitro evolution and other modern approaches; and more.
Full Description
Exploiting the inherent combinatorial mechanism in the biosynthesis of antibodies, an almost limitless variety of biocatalysts may be generated. Catalytic antibodies are capable of performing almost any type of reaction with high selectivity and stereospecificity. Here, the pioneers in the use of catalytic antibodies review the entire scope of this interdisciplinary field, covering such topics as: * theoretical aspects of structure, mechanism and kinetics * practical considerations, from immunization techniques to screening methods * in vitro evolution and other modern approaches * applications from organic synthesis to medical uses. Backed by the leading authorities in antibody catalysis, this is the first book to provide such comprehensive coverage and will be the prime reference for biochemists, organic chemists, biotechnologists and biomedical researchers.
Contents
1 Immunological Evolution of Catalysis (Jun Yin, Peter G. Schultz).1.1 Introduction.1.2 Parallels between Antibody and Enzyme Evolution.1.3 Evolution of Catalytic Antibodies.1.4 Ferrochelatase Antibody 7G12 - Evolution of the Strain Mechanism.1.5 Esterase Antibody 48G7 - Effect of Distant Mutations on Catalysis.1.6 Sulfur Oxidase Antibody 28B4 - Incremental Changes in Evolution.1.7 Oxy-Cope Antibody AZ28 - Evolution of Conformational Diversity in Catalysis.1.8 Diels-Alderase Antibody 39A11 - Evolution of a Polyspecific Antibody combining Site.1.9 Conclusions.References.2 Critical Analysis of Antibody Catalysis (Donald Hilvert).2.1 Introduction.2.2 Exploiting Antibodies as Catalysts.2.3 Catalytic Efficiency.2.4 Hapten Design.2.5 Representative Catalytic Antibodies.2.6 Perspectives.2.7 Conclusions.References.3 Theoretical Studies of Antibody Catalysis (Dean J. Tantillo, Andrew G. Leach, Xiyun Zhang, K. N. Houk).3.1 Introduction.3.2 Questions Subject to Theoretical Elucidation.3.3 Hydrolytic Antibodies.3.4 Cationic Cyclizations.3.5 Antibody-Catalyzed Diels-Alder and retro-Diels-Alder Reactions.3.6 Other Antibody-Catalyzed Pericyclic Reactions.3.7 Antibody-Catalyzed Carboxybenzisoxazole Decarboxylation.3.8 Summary.References.4 The Enterprise of Catalytic Antibodies: A Historical Perspective (Michael Ben-Chaim).4.1 Introduction.4.2 Methods.4.3 Results.4.4 Conclusions.References.5 Catalytic Antibodies in Natural Products Synthesis (Ashraf Brik, Ehud Keinan).5.1 Introduction.5.2 Total Synthesis of a-Multistriatin via Antibody-Catalyzed Asymmetric Protonolysis of an Enol Ether.5.3 Total Synthesis of Epothilones Using Aldolase Antibodies.5.4 Total Synthesis of Brevicomins Using Aldolase Antibody 38C2.5.5 Synthesis of 1-Deoxy-L-Xylose Using 38C2 Antibody.5.6 Synthesis of (+)-Frontalin and Mevalonolactone via Resolution of Tertiary Aldols with 38C2.5.7 Wieland-Miescher Ketone via 38C2-Catalyzed Robinson Annulation.5.8 Formation of Steroid A and B Rings via Cationic Cyclization.5.9 Synthesis of Naproxen via Antibody-Catalyzed Ester Hydrolysis.5.10 Conclusions.References.6 Structure and Function of Catalytic Antibodies (Nicholas A. Larsen, Ian A. Wilson).6.1 Introduction.6.2 Electrostatic Complementarity.6.3 Shape Complementarity and Approximation.6.4 Shape Complementarity and Control of the Reaction Coordinate.6.5 Shape Complementarity and Substrate Strain.6.6 Reactive Amino Acids and the Possibility of Covalent Catalysis.6.7 New Challenges.References.7 Antibody Catalysis of Disfavored Chemical Reactions (Jonathan E. McDunn, Tobin J. Dickerson, Kim D. Janda).7.1 Introduction.7.2 Formal Violation of Baldwin's Rules for Ring Closure: the 6-endo-tet Ring Closure.7.3 Cationic Cyclization.7.4 exo-Diels-Alder Reactions.7.5 Miscellaneous Disfavored Processes.7.6 Summary.References.8 Screening Methods for Catalytic Antibodies (Jean-Louis Reymond).8.1 Introduction.8.2 Theoretical Consideration: What to look for during screening.8.3 A Practical Perspective: Screening in the Published Literature.8.4 High-Throughput Screening Methods.8.5 Examples with Fluorogenic Substrates and Antibodies from Hybridoma.8.6 Conclusion.References.9 In vitro Evolution of Catalytic Antibodies and Other Proteins via Combinatorial Libraries (Ron Piran, Ehud Keinan).9.1 Introduction.9.2 Technologies and Constructs - Basic Principles.9.3 Screening of Libraries.9.4 Directed Evolution.9.5 In vitro Libraries.9.6 In vivo Libraries.9.7 Conclusions and Outlook.References.10 Medicinal Potential of Catalytic Antibodies (Roey Amir, Doron Shabat).10.1 Introduction.10.2 Prodrug Activation.10.3 Cocaine Inactivation.10.4 Conclusions.References.11 Reactive Immunization: A Unique Approach to Aldolase Antibodies (Fujie Tanaka, Carlos F. Barbas, III).11.1 Introduction.11.2 Generation of Aldolase Antibodies by Reactive Immunization.11.3 Structural Insight into Aldolase Antibodies.11.4 Aldolase Antibody-catalyzed Reactions.11.5 Evolution of Aldolase Antibodies in vitro.11.6 Other Catalytic Antibodies Selected with Reactive Compounds in vitro.11.7 Summary.11.8 Acknowledgments.References.12 The Antibody-Catalyzed Water Oxidation Pathway (Cindy Takeuchi, Paul Wentworth Jr.).References.13 Photoenzymes and Photoabzymes (Sigal Saphier, Ron Piran, Ehud Keinan).13.1 Introduction.13.2 Photoenzymes.13.3 Photocatalytic Antibodies.13.4 Conclusions.13.5 Acknowledgement.References.14 Selectivity with Catalytic Antibodies - What Can Be Achieved? (Veronique Gouverneur).14.1 Introduction.14.2 Acyl Transfer Reactions: Ester Hydrolysis, Transacylations, and Amide Hydrolysis.14.3 Glycosyl and Phosphoryl Group Transfer.14.4 Pericyclic Reactions.14.5 Aldol Reactions.14.6 Cyclization.14.6.1 Reduction and Oxidation.14.7 Additions and Eliminations.14.8 Conclusion.References.15 Catalytic Antibodies as Mechanistic and Structural Models of Hydrolytic Enzymes (Ariel B. Lindner, Zelig Eshhar, Dan S. Tawfik).15.1 Introduction.15.2 Chapter Overview.15.3 The Role of Conformational Changes in Catalytic Antibodies.15.4 Conclusions.References.16 Transition State Analogs - Archetype Antigens for Catalytic Antibody Generation (Anita D. Wentworth, Paul Wentworth, Jr., G. Michael Blackburn).References.17 Polyclonal Catalytic Antibodies (Marina Resmini, Elizabeth L. Ostler, Keith Brocklehurst, Gerard Gallacher).17.1 Introduction.17.2 The Importance of Polyclonal Catalytic Antibodies.17.3 Demonstration of Polyclonal Antibody Catalysis.17.4 Hapten Design and Catalytic Antibody Activity.17.5 Kinetic Activity, Homogeneity, and Variability.17.6 Assessment of Contamination.17.7 Mechanistic Studies.17.8 Investigations of Active-Site Availability.17.9 Therapeutic Applications.17.10 Antiidiotypic Antibodies.17.11 Naturally-Occurring Catalytic Antibodies.17.12 Conclusions.References.18 Production of Monoclonal Catalytic Antibodies: Principles and Practice (Diane Kubitz, Ehud Keinan).18.1 Introduction.18.2 Immunization.18.3 Hybridoma Production and Screening.18.4 Large-Scale Antibody Production.18.5 Antibody Purification.18.6 Testing for Catalytic Activity.18.7 Preparation of Fab, F(ab')2, and Fab' Fragments.18.8 Conclusion.References.19 Natural Catalytic Antibodies - Abzymes (Georgy A. Nevinsky, Valentina N. Buneva).19.1 Abbreviations.19.2 Introduction.19.3 Natural Catalytic Antibodies.19.4 Peculiarities of the Immune Status of Patients with Various Autoimmune Diseases.19.5 The Origin of Natural Autoimmune Abzymes.19.6 Peculiarities of the Immune Status of Pregnant and Lactating Women and the Origin of Natural Abzymes from Human Milk.19.7 Purification of Natural Abzymes.19.8 Criteria to Establish that Catalytic Activity is Intrinsic to Antibodies.19.9 Catalytic Antibodies Catalyzing Transformations of Water and Oxygen Radicals.19.10 Antibodies with Proteolytic Activities.19.11 Human and Animal RNase and DNase Abzymes.19.12 Human Milk Abzymes with Various Activities.19.13 Biological Roles of Abzymes.19.14 Natural Abzymes as Tools for Investigating RNA Structure.19.15 Abzymes as Diagnostic Tools and Tools for Biological Manipulations.19.16 Conclusion.References.Index.
