Evaluation of enzyme inhibitors in drug discovery [[electronic resource] ] : a guide for medicinal chemists and pharmacologists / / by Robert A. Copeland |
Autore | Copeland Robert Allen |
Edizione | [2nd ed.] |
Pubbl/distr/stampa | Hoboken, N.J., : Wiley, c2013 |
Descrizione fisica | 1 online resource (572 p.) |
Disciplina | 615/.19 |
Soggetto topico |
Enzyme inhibitors - Therapeutic use - Testing
Drugs - Design Enzyme inhibitors - Structure-activity relationships |
ISBN |
1-118-54039-5
1-299-24215-4 1-118-54040-9 1-118-54028-X |
Formato | Materiale a stampa ![]() |
Livello bibliografico | Monografia |
Lingua di pubblicazione | eng |
Nota di contenuto | Machine generated contents note: Foreword.Preface.Acknowledgments.1. Why Enzymes as Drug Targets?1.1 Enzymes Are Essentials for Life.1.2 Enzyme Structure and Catalysis.1.3 Permutations of Enzyme Structure During Catalysis.1.4 Other Reasons for Studying Enzymes.1.5 Summary.References.2. Enzyme Reaction Mechanisms.2.1 Initial Binding of Substrate.2.2 Noncovalent Forces in Reversible Ligand Binding to Enzymes.2.2.1 Electrostatic Forces.2.2.2 Hydrogen Bonds.2.2.3 Hydrophobic Forces.2.2.4 van der Waals Forces.2.3 Transformations of the Bond Substrate.2.3.1 Strategies for Transition State Stabilization.2.3.2 Enzyme Active Sites Are Most Complementary to the Transition State Structure.2.4 Steady State Analysis of Enzyme Kinetics.2.4.1 Factors Affecting the Steady State Kinetic Constants.2.5 Graphical Determination of kcat and KM2.6 Reactions Involving Multiple Substates.2.6.1 Bisubstrate Reaction Mechanisms.2.7 Summary.References.3. Reversible Modes of Inhibitor Interactions with Enzymes.3.1 Enzyme-Inhibitor Binding Equilibria.3.2 Competitive Inhibition.3.3 Noncompetitive Inhibition.3.3.1 Mutual Exclusively Studies.3.4 Uncompetitive Inhibition.3.5 Inhibition Modality in Bisubstrate Reactions.3.6 Value of Knowing Inhibitor Modality.3.6.1 Quantitative Comparisons of Inhibitor Affinity.3.6.2 Relating Ki to Binding Energy.3.6.3 Defining Target Selectivity by Ki Values.3.6.4 Potential Advantages and Disadvantages of Different Inhibition Modalities In Vivo.3.6.5 Knowing Inhibition Modality Is Important for Structure-Based Lead Organization.3.7 Summary.References.4. Assay Considerations for Compound Library Screening.4.1 Defining Inhibition Signal Robustness, and Hit Criteria.4.2 Measuring Initial Velocity.4.2.1 End-Point and Kinetic Readouts.4.2.2 Effects of Enzyme Concentration.4.3 Balanced Assay Conditions.4.3.1 Balancing Conditions for Multisubstrate Reactions.4.4 Order of Reagent Addition.4.5 Use of Natural Substrates and Enzymes.4.6 Coupled Enzyme Assays.4.7 Hit Validation and Progression.4.8 Summary.References.5. Lead Optimization and Structure-Activity Relationships for Reversible Inhibitors.5.1 Concentration-Response Plots and IC50 Determination.5.1.1 The Hill Coefficient.5.1.2 Graphing and Reporting Concentration-Response Data.5.2 Testing for Reversibility.5.3 Determining Reversible Inhibition Modality and Dissociation Constant.5.4 Comparing Relative Affinity.5.4.1 Compound Selectivity.5.5 Associating Cellular Effects with Target Enzyme Inhibition.5.5.1 Cellular Phenotype Should Be Consistent with Genetic Knockout or Knockdown of the Target Enzyme.5.5.2 Cellular Activity Should Require a Certain Affinity for the target Enzyme.5.5.3 Buildup of Substrate and/or Diminution of Product for the Target Enzyme Should Be Observed in Cells.5.5.4 Cellular Phenotype Should Be Reversed by Cell-Permeable Product or Downstream Metabolites of the Target Enzyme Activity.5.5.5 Mutation of the Target Enzyme Should Lead to Resistance or Hypersensitivity to Inhibitors.5.6 Summary.References.6. Slow Binding Inhibitors.6.1 Determining kobs: The Rate Constant for Onset of Inhibition.6.2 Mechanisms of Slow Binding Inhibition.6.3 Determination of Mechanism and Assessment of True Affinity.6.3.1 Potential Clinical Advantages of Slow Off-rate Inhibitors.6.4 Determining Inhibition Modality for Slow Binding Inhibitors.6.5 SAR for Slow Binding Inhibitors.6.6 Some Examples of Pharmacologically Interesting Slow Binding Inhibitors.6.6.1 Examples of Scheme B: Inhibitors of Zinc Peptidases and Proteases.6.6.2 Example of Scheme C: Inhibition of Dihydrofolate Reductase by Methotresate.6.6.3 Example of Scheme C: Inhibition of Calcineurin by FKBP-Inhibitor Complexes.6.6.4 Example of Scheme C When Ki* << Ki: Aspartyl Protease Inhibitors.6.6.5 Example of Scheme C When k6 Is Very Small: Selective COX2 Inhibitors.6.7 Summary.References.7. Tight Binding Inhibitors.7.1 Effects of Tight Binding Inhibition Concentration-Response Data.7.2 The IC50 Value Depends on Kiapp and [E]T.7.3 Morrison's Quadratic Equation for Fiting Concentration-Response Data for Tight Binding Inhibitors.7.3.1 Optimizing Conditions for Kiapp Determination Using Morrison's Equation.7.3.2 Limits on Kiapp Determinations.7.3.3 Use of a Cubic Equation When Both Substrate and Inhibitor Are Tight Binding.7.4 Determining Modality for Tight Binding Enzyme Inhibitors.7.5 Tight Binding Inhibitors Often Display Slow Binding Behavior.7.6 Practical Approaches to Overcoming the Tight Binding Limit in Determine Ki.7.7 Enzyme-Reaction Intermediate Analogues as Example of Tight Binding Inhibitors.7.7.1 Bisubstrate Analogues.7.7.2 Testing for Transition State Mimicry.7.8 Potential Clinical Advantages of Tight Binding Inhibitors.7.9 Determination of [E]T Using Tight Binding Inhibitors.7.10 Summary.References.8. Irreversible Enzyme Inactivators.8.1 Kinetic Evaluation of Irreversible Enzyme Inactivators.8.2 Affinity Labels.8.2.1 Quiescent Affinity Labels.8.2.2 Potential Liabilities of Affinity Labels as Drugs.8.3 Mechanism-Based Inactivators.8.3.1 Distinguishing Features of Mechanism-Based Inactivation.8.3.2 Determination of the Partition Ratio.8.3.3 Potential Clinical Advantages of Mechanism-Based Inactivators.8.3.4 Examples of Mechanism-Based Inactivators as Drugs.8.4 Use of Affinity Labels as Mechanistic Tools.8.5 Summary.References.Appendix 1. Kinetic of Biochemical Reactions.A1.1 The Law of Mass Action and Reaction Order.A1.2 First-Order Reaction Kinetics.A1.3 Second-Order Reaction Kinetics.A1.4 Pseudo-First-Order Reaction Conditions.A1.5 Approach to Equilibrium: An Example of the Kinetics of Reversible Reactions.References.Appendix 2. Derivation of the Enzyme-Ligand Binding Isotherm Equation.References.Appendix 3. Serial Dilution Schemes.Index. |
Record Nr. | UNINA-9910141602903321 |
Copeland Robert Allen
![]() |
||
Hoboken, N.J., : Wiley, c2013 | ||
![]() | ||
Lo trovi qui: Univ. Federico II | ||
|
Evaluation of enzyme inhibitors in drug discovery [[electronic resource] ] : a guide for medicinal chemists and pharmacologists / / by Robert A. Copeland |
Autore | Copeland Robert Allen |
Edizione | [2nd ed.] |
Pubbl/distr/stampa | Hoboken, N.J., : Wiley, c2013 |
Descrizione fisica | 1 online resource (572 p.) |
Disciplina | 615/.19 |
Soggetto topico |
Enzyme inhibitors - Therapeutic use - Testing
Drugs - Design Enzyme inhibitors - Structure-activity relationships |
ISBN |
1-118-54039-5
1-299-24215-4 1-118-54040-9 1-118-54028-X |
Formato | Materiale a stampa ![]() |
Livello bibliografico | Monografia |
Lingua di pubblicazione | eng |
Nota di contenuto | Machine generated contents note: Foreword.Preface.Acknowledgments.1. Why Enzymes as Drug Targets?1.1 Enzymes Are Essentials for Life.1.2 Enzyme Structure and Catalysis.1.3 Permutations of Enzyme Structure During Catalysis.1.4 Other Reasons for Studying Enzymes.1.5 Summary.References.2. Enzyme Reaction Mechanisms.2.1 Initial Binding of Substrate.2.2 Noncovalent Forces in Reversible Ligand Binding to Enzymes.2.2.1 Electrostatic Forces.2.2.2 Hydrogen Bonds.2.2.3 Hydrophobic Forces.2.2.4 van der Waals Forces.2.3 Transformations of the Bond Substrate.2.3.1 Strategies for Transition State Stabilization.2.3.2 Enzyme Active Sites Are Most Complementary to the Transition State Structure.2.4 Steady State Analysis of Enzyme Kinetics.2.4.1 Factors Affecting the Steady State Kinetic Constants.2.5 Graphical Determination of kcat and KM2.6 Reactions Involving Multiple Substates.2.6.1 Bisubstrate Reaction Mechanisms.2.7 Summary.References.3. Reversible Modes of Inhibitor Interactions with Enzymes.3.1 Enzyme-Inhibitor Binding Equilibria.3.2 Competitive Inhibition.3.3 Noncompetitive Inhibition.3.3.1 Mutual Exclusively Studies.3.4 Uncompetitive Inhibition.3.5 Inhibition Modality in Bisubstrate Reactions.3.6 Value of Knowing Inhibitor Modality.3.6.1 Quantitative Comparisons of Inhibitor Affinity.3.6.2 Relating Ki to Binding Energy.3.6.3 Defining Target Selectivity by Ki Values.3.6.4 Potential Advantages and Disadvantages of Different Inhibition Modalities In Vivo.3.6.5 Knowing Inhibition Modality Is Important for Structure-Based Lead Organization.3.7 Summary.References.4. Assay Considerations for Compound Library Screening.4.1 Defining Inhibition Signal Robustness, and Hit Criteria.4.2 Measuring Initial Velocity.4.2.1 End-Point and Kinetic Readouts.4.2.2 Effects of Enzyme Concentration.4.3 Balanced Assay Conditions.4.3.1 Balancing Conditions for Multisubstrate Reactions.4.4 Order of Reagent Addition.4.5 Use of Natural Substrates and Enzymes.4.6 Coupled Enzyme Assays.4.7 Hit Validation and Progression.4.8 Summary.References.5. Lead Optimization and Structure-Activity Relationships for Reversible Inhibitors.5.1 Concentration-Response Plots and IC50 Determination.5.1.1 The Hill Coefficient.5.1.2 Graphing and Reporting Concentration-Response Data.5.2 Testing for Reversibility.5.3 Determining Reversible Inhibition Modality and Dissociation Constant.5.4 Comparing Relative Affinity.5.4.1 Compound Selectivity.5.5 Associating Cellular Effects with Target Enzyme Inhibition.5.5.1 Cellular Phenotype Should Be Consistent with Genetic Knockout or Knockdown of the Target Enzyme.5.5.2 Cellular Activity Should Require a Certain Affinity for the target Enzyme.5.5.3 Buildup of Substrate and/or Diminution of Product for the Target Enzyme Should Be Observed in Cells.5.5.4 Cellular Phenotype Should Be Reversed by Cell-Permeable Product or Downstream Metabolites of the Target Enzyme Activity.5.5.5 Mutation of the Target Enzyme Should Lead to Resistance or Hypersensitivity to Inhibitors.5.6 Summary.References.6. Slow Binding Inhibitors.6.1 Determining kobs: The Rate Constant for Onset of Inhibition.6.2 Mechanisms of Slow Binding Inhibition.6.3 Determination of Mechanism and Assessment of True Affinity.6.3.1 Potential Clinical Advantages of Slow Off-rate Inhibitors.6.4 Determining Inhibition Modality for Slow Binding Inhibitors.6.5 SAR for Slow Binding Inhibitors.6.6 Some Examples of Pharmacologically Interesting Slow Binding Inhibitors.6.6.1 Examples of Scheme B: Inhibitors of Zinc Peptidases and Proteases.6.6.2 Example of Scheme C: Inhibition of Dihydrofolate Reductase by Methotresate.6.6.3 Example of Scheme C: Inhibition of Calcineurin by FKBP-Inhibitor Complexes.6.6.4 Example of Scheme C When Ki* << Ki: Aspartyl Protease Inhibitors.6.6.5 Example of Scheme C When k6 Is Very Small: Selective COX2 Inhibitors.6.7 Summary.References.7. Tight Binding Inhibitors.7.1 Effects of Tight Binding Inhibition Concentration-Response Data.7.2 The IC50 Value Depends on Kiapp and [E]T.7.3 Morrison's Quadratic Equation for Fiting Concentration-Response Data for Tight Binding Inhibitors.7.3.1 Optimizing Conditions for Kiapp Determination Using Morrison's Equation.7.3.2 Limits on Kiapp Determinations.7.3.3 Use of a Cubic Equation When Both Substrate and Inhibitor Are Tight Binding.7.4 Determining Modality for Tight Binding Enzyme Inhibitors.7.5 Tight Binding Inhibitors Often Display Slow Binding Behavior.7.6 Practical Approaches to Overcoming the Tight Binding Limit in Determine Ki.7.7 Enzyme-Reaction Intermediate Analogues as Example of Tight Binding Inhibitors.7.7.1 Bisubstrate Analogues.7.7.2 Testing for Transition State Mimicry.7.8 Potential Clinical Advantages of Tight Binding Inhibitors.7.9 Determination of [E]T Using Tight Binding Inhibitors.7.10 Summary.References.8. Irreversible Enzyme Inactivators.8.1 Kinetic Evaluation of Irreversible Enzyme Inactivators.8.2 Affinity Labels.8.2.1 Quiescent Affinity Labels.8.2.2 Potential Liabilities of Affinity Labels as Drugs.8.3 Mechanism-Based Inactivators.8.3.1 Distinguishing Features of Mechanism-Based Inactivation.8.3.2 Determination of the Partition Ratio.8.3.3 Potential Clinical Advantages of Mechanism-Based Inactivators.8.3.4 Examples of Mechanism-Based Inactivators as Drugs.8.4 Use of Affinity Labels as Mechanistic Tools.8.5 Summary.References.Appendix 1. Kinetic of Biochemical Reactions.A1.1 The Law of Mass Action and Reaction Order.A1.2 First-Order Reaction Kinetics.A1.3 Second-Order Reaction Kinetics.A1.4 Pseudo-First-Order Reaction Conditions.A1.5 Approach to Equilibrium: An Example of the Kinetics of Reversible Reactions.References.Appendix 2. Derivation of the Enzyme-Ligand Binding Isotherm Equation.References.Appendix 3. Serial Dilution Schemes.Index. |
Record Nr. | UNINA-9910808406303321 |
Copeland Robert Allen
![]() |
||
Hoboken, N.J., : Wiley, c2013 | ||
![]() | ||
Lo trovi qui: Univ. Federico II | ||
|
Evaluation of enzyme inhibitors in drug discovery [[electronic resource] ] : a guide for medicinal chemists and pharmacologists / / Robert A. Copeland |
Autore | Copeland Robert Allen |
Pubbl/distr/stampa | Hoboken, N.J., : Wiley-Interscience, 2005 |
Descrizione fisica | xvii, 271 p. : ill |
Disciplina | 615/.19 |
Collana | Methods of biochemical analysis |
Soggetto topico |
Enzyme inhibitors - Therapeutic use - Testing
Drugs - Design Enzyme inhibitors - Structure-activity relationships |
Soggetto genere / forma | Electronic books. |
ISBN |
0-471-72327-4
1-280-25506-4 9786610255061 0-471-72326-6 |
Formato | Materiale a stampa ![]() |
Livello bibliografico | Monografia |
Lingua di pubblicazione | eng |
Record Nr. | UNINA-9910449948503321 |
Copeland Robert Allen
![]() |
||
Hoboken, N.J., : Wiley-Interscience, 2005 | ||
![]() | ||
Lo trovi qui: Univ. Federico II | ||
|
Evaluation of enzyme inhibitors in drug discovery [[electronic resource] ] : a guide for medicinal chemists and pharmacologists / / Robert A. Copeland |
Autore | Copeland Robert Allen |
Pubbl/distr/stampa | Hoboken, N.J., : Wiley-Interscience, 2005 |
Descrizione fisica | xvii, 271 p. : ill |
Disciplina | 615/.19 |
Collana | Methods of biochemical analysis |
Soggetto topico |
Enzyme inhibitors - Therapeutic use - Testing
Drugs - Design Enzyme inhibitors - Structure-activity relationships |
ISBN |
0-471-72327-4
1-280-25506-4 9786610255061 0-471-72326-6 |
Formato | Materiale a stampa ![]() |
Livello bibliografico | Monografia |
Lingua di pubblicazione | eng |
Record Nr. | UNINA-9910783520003321 |
Copeland Robert Allen
![]() |
||
Hoboken, N.J., : Wiley-Interscience, 2005 | ||
![]() | ||
Lo trovi qui: Univ. Federico II | ||
|
Evaluation of enzyme inhibitors in drug discovery [[electronic resource] ] : a guide for medicinal chemists and pharmacologists / / Robert A. Copeland |
Autore | Copeland Robert Allen |
Edizione | [1st ed.] |
Pubbl/distr/stampa | Hoboken, N.J., : Wiley-Interscience, 2005 |
Descrizione fisica | xvii, 271 p. : ill |
Disciplina | 615/.19 |
Collana | Methods of biochemical analysis |
Soggetto topico |
Enzyme inhibitors - Therapeutic use - Testing
Drugs - Design Enzyme inhibitors - Structure-activity relationships |
ISBN |
0-471-72327-4
1-280-25506-4 9786610255061 0-471-72326-6 |
Formato | Materiale a stampa ![]() |
Livello bibliografico | Monografia |
Lingua di pubblicazione | eng |
Nota di contenuto |
Intro -- Evaluation of Enzyme Inhibitors in Drug Discovery -- Contents -- Foreword -- Preface -- Acknowledgments -- 1. Why Enzymes as Drug Targets? -- 1.1 Enzymes Are Essential for Life -- 1.2 Enzyme Structure and Catalysis -- 1.3 Permutations of Enzyme Structure during Catalysis -- 1.4 Other Reasons for Studying Enzymes -- 1.5 Summary -- References -- 2. Enzyme Reaction Mechanisms -- 2.1 Initial Binding of Substrate -- 2.2 Noncovalent Forces in Reversible Ligand Binding to Enzymes -- 2.2.1 Electrostatic Forces -- 2.2.2 Hydrogen Bonds -- 2.2.3 Hydrophobic Forces -- 2.2.4 van der Waals Forces -- 2.3 Transformations of the Bound Substrate -- 2.3.1 Strategies for Transition State Stabilization -- 2.3.2 Enzyme Active Sites Are Most Complementary to the Transition State Structure -- 2.4 Steady State Analysis of Enzyme Kinetics -- 2.4.1 Factors Affecting the Steady State Kinetic Constants -- 2.5 Graphical Determination of k(cat) and K(M) -- 2.6 Reactions Involving Multiple Substrates -- 2.6.1 Bisubstrate Reaction Mechanisms -- 2.7 Summary -- References -- 3. Reversible Modes of Inhibitor Interactions with Enzymes -- 3.1 Enzyme-Inhibitor Binding Equilibria -- 3.2 Competitive Inhibition -- 3.3 Noncompetititive Inhibition -- 3.3.1 Mutual Exclusivity Studies -- 3.4 Uncompetitive Inhibition -- 3.5 Inhibition Modality in Bisubstrate Reactions -- 3.6 Value of Knowing Inhibitor Modality -- 3.6.1 Quantitative Comparisons of Inhibitor Affinity -- 3.6.2 Relating K(i) to Binding Energy -- 3.6.3 Defining Target Selectivity by K(i) Values -- 3.6.4 Potential Advantages and Disadvantages of Different Inhibition Modalities In Vivo -- 3.6.5 Knowing Inhibition Modality Is Important for Structure-Based Lead Optimization -- 3.7 Summary -- References -- 4. Assay Considerations for Compound Library Screening -- 4.1 Defining Inhibition, Signal Robustness, and Hit Criteria.
4.2 Measuring Initial Velocity -- 4.2.1 End-Point and Kinetic Readouts -- 4.2.2 Effects of Enzyme Concentration -- 4.2.3 Other Factors Affecting Initial Velocity -- 4.3 Balanced Assay Conditions -- 4.3.1 Balancing Conditions for Multisubstrate Reactions -- 4.4 Order of Reagent Addition -- 4.5 Use of Natural Substrates and Enzymes -- 4.6 Coupled Enzyme Assays -- 4.7 Hit Validation and Progression -- 4.8 Summary -- References -- 5. Lead Optimization and Structure-Activity Relationships for Reversible Inhibitors -- 5.1 Concentration-Response Plots and IC(50) Determination -- 5.1.1 The Hill Coefficient -- 5.1.2 Graphing and Reporting Concentration-Response Data -- 5.2 Testing for Reversibility -- 5.3 Determining Reversible Inhibition Modality and Dissociation Constant -- 5.4 Comparing Relative Affinity -- 5.4.1 Compound Selectivity -- 5.5 Associating Cellular Effects with Target Enzyme Inhibition -- 5.5.1 Cellular Phenotype Should Be Consistent with Genetic Knockout or Knockdown of the Target Enzyme -- 5.5.2 Cellular Activity Should Require a Certain Affinity for the Target Enzyme -- 5.5.3 Buildup of Substrate and/or Diminution of Product for the Target Enzyme Should Be Observed in Cells -- 5.5.4 Cellular Phenotype Should Be Reversed by Cell-Permeable Product or Downstream Metabolites of the Target Enzyme Activity -- 5.5.5 Mutation of the Target Enzyme Should Lead to Resistance or Hypersensitivity to Inhibitors -- 5.6 Summary -- References -- 6. Slow Binding Inhibitors -- 6.1 Determining k(obs): The Rate Constant for Onset of Inhibition -- 6.2 Mechanisms of Slow Binding Inhibition -- 6.3 Determination of Mechanism and Assessment of True Affinity -- 6.3.1 Potential Clinical Advantages of Slow Off-rate Inhibitors -- 6.4 Determining Inhibition Modality for Slow Binding Inhibitors -- 6.5 SAR for Slow Binding Inhibitors. 6.6 Some Examples of Pharmacologically Interesting Slow Binding Inhibitors -- 6.6.1 Examples of Scheme B: Inhibitors of Zinc Peptidases and Proteases -- 6.6.2 Example of Scheme C: Inhibition of Dihydrofolate Reductase by Methotrexate -- 6.6.3 Example of Scheme C: Inhibition of Calcineurin by FKBP-Inhibitor Complexes -- 6.6.4 Example of Scheme C When K*(i) < -- < -- K(i): Aspartyl Protease Inhibitors -- 6.6.5 Example of Scheme C When k(6) Is Very Small: Selective COX2 Inhibitors -- 6.7 Summary -- References -- 7. Tight Binding Inhibitors -- 7.1 Effects of Tight Binding Inhibition Concentration-Response Data -- 7.2 The IC(50) Value Depends on K(app)(i) and [E](T) -- 7.3 Morrison's Quadratic Equation for Fitting Concentration-Response Data for Tight Binding Inhibitors -- 7.3.1 Optimizing Conditions for K(app)(i) Determination Using Morrison's Equation -- 7.3.2 Limits on K(app)(i) Determinations -- 7.3.3 Use of a Cubic Equation When Both Substrate and Inhibitor Are Tight Binding -- 7.4 Determining Modality for Tight Binding Enzyme Inhibitors -- 7.5 Tight Binding Inhibitors Often Display Slow Binding Behavior -- 7.6 Practical Approaches to Overcoming the Tight Binding Limit in Determining K(i) -- 7.7 Enzyme-Reaction Intermediate Analogues as Examples of Tight Binding Inhibitors -- 7.7.1 Bisubstrate Analogues -- 7.7.2 Testing for Transition State Mimicry -- 7.8 Potential Clinical Advantages of Tight Binding Inhibitors -- 7.9 Determination of [E](T) Using Tight Binding Inhibitors -- 7.10 Summary -- References -- 8. Irreversible Enzyme Inactivators -- 8.1 Kinetic Evaluation of Irreversible Enzyme Inactivators -- 8.2 Affinity Labels -- 8.2.1 Quiescent Affinity Labels -- 8.2.2 Potential Liabilities of Affinity Labels as Drugs -- 8.3 Mechanism-Based Inactivators -- 8.3.1 Distinguishing Features of Mechanism-Based Inactivation. 8.3.2 Determination of the Partition Ratio -- 8.3.3 Potential Clinical Advantages of Mechanism-Based Inactivators -- 8.3.4 Examples of Mechanism-Based Inactivators as Drugs -- 8.4 Use of Affinity Labels as Mechanistic Tools -- 8.5 Summary -- References -- Appendix 1. Kinetics of Biochemical Reactions -- A1.1 The Law of Mass Action and Reaction Order -- A1.2 First-Order Reaction Kinetics -- A1.3 Second-Order Reaction Kinetics -- A1.4 Pseudo-First-Order Reaction Conditions -- A1.5 Approach to Equilibrium: An Example of the Kinetics of Reversible Reactions -- References -- Appendix 2. Derivation of the Enzyme-Ligand Binding Isotherm Equation -- References -- Appendix 3. Serial Dilution Schemes -- Index. |
Record Nr. | UNINA-9910827528903321 |
Copeland Robert Allen
![]() |
||
Hoboken, N.J., : Wiley-Interscience, 2005 | ||
![]() | ||
Lo trovi qui: Univ. Federico II | ||
|