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Molecular Interaction Fields [[electronic resource] ] : Applications in Drug Discovery and ADME Prediction
| Molecular Interaction Fields [[electronic resource] ] : Applications in Drug Discovery and ADME Prediction |
| Autore | Cruciani Gabriele |
| Pubbl/distr/stampa | Hoboken, : Wiley, 2006 |
| Descrizione fisica | 1 online resource (323 p.) |
| Disciplina | 615.19 |
| Altri autori (Persone) |
MannholdRaimund
KubinyiHugo FolkersGerd |
| Collana | Methods and Principles in Medicinal Chemistry |
| Soggetto topico |
Biomolecules
Chemical reactions -- Computer simulation Chemicals -- Pharmacokinetics -- Forecasting Chemicals -- Physiological effect -- Forecasting Drug development Pharmaceutical chemistry Structure-activity relationships (Biochemistry) -- Computer simulation Pharmaceutical chemistry - Physiological effect - Forecasting Chemicals - Computer simulation Chemical reactions - Computer simulation Structure-activity relationships (Biochemistry) Computational Biology Models, Molecular Quantitative Structure-Activity Relationship Computer Simulation Drug Design Pharmaceutical Preparations Software Structure-Activity Relationship Biology Drug Discovery Computing Methodologies Chemicals and Drugs Models, Theoretical Biological Science Disciplines Chemistry, Pharmaceutical Biochemical Phenomena Information Science Pharmacological Phenomena Investigative Techniques Natural Science Disciplines Analytical, Diagnostic and Therapeutic Techniques and Equipment Pharmacology Physiological Phenomena Chemistry Chemical Phenomena Phenomena and Processes Disciplines and Occupations Pharmacy, Therapeutics, & Pharmacology History of Medicine Health & Biological Sciences Medicine |
| Soggetto genere / forma | Electronic books. |
| ISBN |
1-280-85421-9
9786610854219 3-527-60767-6 3-527-60713-7 |
| Formato | Materiale a stampa  |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto |
Molecular Interaction Fields; A Personal Foreword; Contents; Preface; List of Contributors; I Introduction; 1 The Basic Principles of GRID; 1.1 Introduction; 1.2 Philosophy and Objectives; 1.3 Priorities; 1.4 The GRID Method; 1.4.1 GRID Probes Are Anisometric; 1.4.2 The Target "Responds" to the Probe; 1.4.3 The Target is Immersed in Water; 1.5 The GRID Force Field; 1.5.1 The Lennard-Jones Term; 1.5.2 The Electrostatic Term; 1.5.3 The Hydrogen Bond Term; 1.5.4 The Other Terms; 1.6 Nomenclature; 1.6.1 "ATOM" Records; 1.6.2 "HETATM" Records; 1.7 Calibrating the GRID Force Field
1.7.1 Checking the Calibration1.7.2 Checking Datafile GRUB; 1.8 The Output from GRID; 1.8.1 GRID Maps from Macromolecules; 1.8.2 GRID Maps from a Small Molecule; 1.9 Conclusions; 2 Calculation and Application of Molecular Interaction Fields; 2.1 Introduction; 2.2 Calculation of MIFs; 2.2.1 The Target; 2.2.2 The Probe; 2.2.3 The Interaction Function; 2.2.3.1 Van der Waals Interactions; 2.2.3.2 Electrostatic Interactions; 2.2.3.3 Hydrogen Bonds; 2.2.3.4 Entropy; 2.3 Selected Applications of MIFs; 2.3.1 Mapping a Ligand Binding Site in a Protein; 2.3.2 Deriving 3D-QSARs 2.3.3 Similarity Analysis of a Set of Related Molecules2.4 Concluding Remarks and Outlook; II Pharmacodynamics; 3 Protein Selectivity Studies Using GRID-MIFs; 3.1 Introduction; 3.2 GRID Calculations and Chemometric Analysis; 3.2.1 Source and Selection of Target Structures; 3.2.2 Selection and Superimposition of Binding Sites; 3.2.3 Calculation of the Molecular Interaction Field; 3.2.4 Matrix Generation and Pretreatments; 3.2.4.1 Region Cut-outs; 3.2.5 GRID/PCA; 3.2.5.1 Score Plots; 3.2.5.2 Two-Dimensional Loading Plots; 3.2.5.3 Loading Contour Maps; 3.2.5.4 Problems of GRID/PCA 3.2.6 GRID/CPCA3.2.6.1 Block Unscaled Weights; 3.2.6.2 CPCA; 3.2.6.3 Identification of Important Variable Blocks for Selectivity; 3.2.6.4 Contour Plots; 3.3 Applications; 3.3.1 DNA Minor Groove Binding - Compare AAA and GGG Double Helix; 3.3.2 Dihydrofolate Reductase; 3.3.3 Cyclooxygenase; 3.3.4 Penicillin Acylase; 3.3.5 Serine Proteases; 3.3.5.1 S1 Pocket; 3.3.5.2 P Pocket; 3.3.5.3 D Pocket; 3.3.6 CYP450; 3.3.7 Target Family Landscapes of Protein Kinases; 3.3.8 Matrix Metalloproteinases (MMPs); 3.3.9 Nitric Oxide Synthases; 3.3.10 PPARs; 3.3.11 Bile Acid Transportation System 3.3.12 Ephrin Ligands and Eph Kinases3.4 Discussion and Conclusion; 4 FLAP: 4-Point Pharmacophore Fingerprints from GRID; 4.1 Introduction; 4.1.1 Pharmacophores and Pharmacophore Fingerprints; 4.1.2 FLAP; 4.2 FLAP Theory; 4.3 Docking; 4.3.1 GLUE: A New Docking Program Based on Pharmacophores; 4.3.2 Case Study; 4.4 Structure Based Virtual Screening (SBVS); 4.5 Ligand Based Virtual Screening (LBVS); 4.6 Protein Similarity; 4.7 TOPP (Triplets of Pharmacophoric Points); 4.8 Conclusions; 5 The Complexity of Molecular Interaction: Molecular Shape Fingerprints by the PathFinder Approach 5.1 Introduction |
| Record Nr. | UNINA-9910144275303321 |
Cruciani Gabriele
|
||
| Hoboken, : Wiley, 2006 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Molecular Interaction Fields [[electronic resource] ] : Applications in Drug Discovery and ADME Prediction
| Molecular Interaction Fields [[electronic resource] ] : Applications in Drug Discovery and ADME Prediction |
| Autore | Cruciani Gabriele |
| Pubbl/distr/stampa | Hoboken, : Wiley, 2006 |
| Descrizione fisica | 1 online resource (323 p.) |
| Disciplina | 615.19 |
| Altri autori (Persone) |
MannholdRaimund
KubinyiHugo FolkersGerd |
| Collana | Methods and Principles in Medicinal Chemistry |
| Soggetto topico |
Biomolecules
Chemical reactions -- Computer simulation Chemicals -- Pharmacokinetics -- Forecasting Chemicals -- Physiological effect -- Forecasting Drug development Pharmaceutical chemistry Structure-activity relationships (Biochemistry) -- Computer simulation Pharmaceutical chemistry - Physiological effect - Forecasting Chemicals - Computer simulation Chemical reactions - Computer simulation Structure-activity relationships (Biochemistry) Computational Biology Models, Molecular Quantitative Structure-Activity Relationship Computer Simulation Drug Design Pharmaceutical Preparations Software Structure-Activity Relationship Biology Drug Discovery Computing Methodologies Chemicals and Drugs Models, Theoretical Biological Science Disciplines Chemistry, Pharmaceutical Biochemical Phenomena Information Science Pharmacological Phenomena Investigative Techniques Natural Science Disciplines Analytical, Diagnostic and Therapeutic Techniques and Equipment Pharmacology Physiological Phenomena Chemistry Chemical Phenomena Phenomena and Processes Disciplines and Occupations Pharmacy, Therapeutics, & Pharmacology History of Medicine Health & Biological Sciences Medicine |
| ISBN |
1-280-85421-9
9786610854219 3-527-60767-6 3-527-60713-7 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto |
Molecular Interaction Fields; A Personal Foreword; Contents; Preface; List of Contributors; I Introduction; 1 The Basic Principles of GRID; 1.1 Introduction; 1.2 Philosophy and Objectives; 1.3 Priorities; 1.4 The GRID Method; 1.4.1 GRID Probes Are Anisometric; 1.4.2 The Target "Responds" to the Probe; 1.4.3 The Target is Immersed in Water; 1.5 The GRID Force Field; 1.5.1 The Lennard-Jones Term; 1.5.2 The Electrostatic Term; 1.5.3 The Hydrogen Bond Term; 1.5.4 The Other Terms; 1.6 Nomenclature; 1.6.1 "ATOM" Records; 1.6.2 "HETATM" Records; 1.7 Calibrating the GRID Force Field
1.7.1 Checking the Calibration1.7.2 Checking Datafile GRUB; 1.8 The Output from GRID; 1.8.1 GRID Maps from Macromolecules; 1.8.2 GRID Maps from a Small Molecule; 1.9 Conclusions; 2 Calculation and Application of Molecular Interaction Fields; 2.1 Introduction; 2.2 Calculation of MIFs; 2.2.1 The Target; 2.2.2 The Probe; 2.2.3 The Interaction Function; 2.2.3.1 Van der Waals Interactions; 2.2.3.2 Electrostatic Interactions; 2.2.3.3 Hydrogen Bonds; 2.2.3.4 Entropy; 2.3 Selected Applications of MIFs; 2.3.1 Mapping a Ligand Binding Site in a Protein; 2.3.2 Deriving 3D-QSARs 2.3.3 Similarity Analysis of a Set of Related Molecules2.4 Concluding Remarks and Outlook; II Pharmacodynamics; 3 Protein Selectivity Studies Using GRID-MIFs; 3.1 Introduction; 3.2 GRID Calculations and Chemometric Analysis; 3.2.1 Source and Selection of Target Structures; 3.2.2 Selection and Superimposition of Binding Sites; 3.2.3 Calculation of the Molecular Interaction Field; 3.2.4 Matrix Generation and Pretreatments; 3.2.4.1 Region Cut-outs; 3.2.5 GRID/PCA; 3.2.5.1 Score Plots; 3.2.5.2 Two-Dimensional Loading Plots; 3.2.5.3 Loading Contour Maps; 3.2.5.4 Problems of GRID/PCA 3.2.6 GRID/CPCA3.2.6.1 Block Unscaled Weights; 3.2.6.2 CPCA; 3.2.6.3 Identification of Important Variable Blocks for Selectivity; 3.2.6.4 Contour Plots; 3.3 Applications; 3.3.1 DNA Minor Groove Binding - Compare AAA and GGG Double Helix; 3.3.2 Dihydrofolate Reductase; 3.3.3 Cyclooxygenase; 3.3.4 Penicillin Acylase; 3.3.5 Serine Proteases; 3.3.5.1 S1 Pocket; 3.3.5.2 P Pocket; 3.3.5.3 D Pocket; 3.3.6 CYP450; 3.3.7 Target Family Landscapes of Protein Kinases; 3.3.8 Matrix Metalloproteinases (MMPs); 3.3.9 Nitric Oxide Synthases; 3.3.10 PPARs; 3.3.11 Bile Acid Transportation System 3.3.12 Ephrin Ligands and Eph Kinases3.4 Discussion and Conclusion; 4 FLAP: 4-Point Pharmacophore Fingerprints from GRID; 4.1 Introduction; 4.1.1 Pharmacophores and Pharmacophore Fingerprints; 4.1.2 FLAP; 4.2 FLAP Theory; 4.3 Docking; 4.3.1 GLUE: A New Docking Program Based on Pharmacophores; 4.3.2 Case Study; 4.4 Structure Based Virtual Screening (SBVS); 4.5 Ligand Based Virtual Screening (LBVS); 4.6 Protein Similarity; 4.7 TOPP (Triplets of Pharmacophoric Points); 4.8 Conclusions; 5 The Complexity of Molecular Interaction: Molecular Shape Fingerprints by the PathFinder Approach 5.1 Introduction |
| Record Nr. | UNINA-9910829869103321 |
|
Cruciani Gabriele
|
||
| Hoboken, : Wiley, 2006 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
RNA As a Drug Target : The Next Frontier for Medicinal Chemistry
| RNA As a Drug Target : The Next Frontier for Medicinal Chemistry |
| Autore | Schneekloth John |
| Edizione | [1st ed.] |
| Pubbl/distr/stampa | Newark : , : John Wiley & Sons, Incorporated, , 2024 |
| Descrizione fisica | 1 online resource (411 pages) |
| Altri autori (Persone) |
PetterssonMartin
MannholdRaimund BuschmannHelmut HolenzJörg |
| Collana | Methods and Principles in Medicinal Chemistry Series |
| ISBN |
9783527840434
9783527351008 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto |
Cover -- Title Page -- Copyright -- Contents -- Series Editors' Preface -- Preface -- Chapter 1 Introduction -- References -- Chapter 2 RNA Structure Probing, Dynamics, and Folding -- 2.1 Introduction -- 2.1.1 Relevance of RNA Structure in Disease -- 2.1.2 Challenges in Studying RNA Structures -- 2.2 Experimentally Guided RNA Structure Modeling -- 2.2.1 Structural Interrogation of RNA Nucleotides via Chemical Probing -- 2.2.1.1 Limits of RNA Chemical Probing -- 2.2.2 Direct Mapping of RNA-RNA Interactions -- 2.2.2.1 Limits of RNA-RNA Interaction Mapping -- 2.2.3 Mapping Spatially Proximal Nucleotides in RNA molecules -- 2.2.3.1 Limits of Methods for Spatial Proximity Mapping -- 2.3 Dealing with RNA Structure Heterogeneity -- 2.4 Querying RNA-Small Molecule Interactions with Chemical Probing -- 2.5 Conclusions and Future Prospects -- References -- Chapter 3 High‐Resolution Structures of RNA -- 3.1 Introduction -- 3.2 X‐Ray Crystallography -- 3.3 NMR Spectroscopy -- 3.4 Cryo‐EM -- 3.5 3D Structure Prediction and Integrative Approaches -- 3.6 Conclusions -- Acknowledgments -- Conflicts of Interest -- References -- Chapter 4 Screening and Lead Generation Techniques for RNA Binders -- 4.1 Knowledge‐Based Versus Agnostic Screening -- 4.2 Virtual Screening -- 4.3 Screening Methods -- 4.3.1 High‐Throughput Screening (HTS) -- 4.3.1.1 Mass Spectrometry -- 4.3.1.2 HTS of RNA Using Direct MS Approaches -- 4.3.1.3 HTS of RNA Using Indirect MS Approaches -- 4.3.1.4 DNA‐Encoded Libraries (DELs) -- 4.3.1.5 Microarray Screening -- 4.3.1.6 Fragment‐Based Drug Discovery -- 4.3.1.7 Phage Display -- 4.3.2 Orthogonal Methods -- 4.3.2.1 Surface Plasmon Resonance -- 4.3.2.2 Fluorescence‐Based Assays -- 4.3.2.3 Microscale Thermophoresis (MST) -- 4.3.2.4 Isothermal Titration Calorimetry (ITC) -- 4.4 Binding Site Identification/Target Engagement -- 4.4.1 Covalent Methods.
4.4.2 Competition with an Antisense Oligonucleotide (ASO) -- 4.5 Defining SAR and Functional Assays -- 4.5.1 Functional Assays -- 4.5.2 Phenotypic Screens -- 4.6 Identifying a Lead Series -- 4.6.1 Hit Optimization -- 4.6.2 Risdiplam Hit‐to‐Lead -- 4.6.3 Branaplam Lead Generation -- 4.6.4 Zotatifin Lead Generation -- 4.7 Concluding Thoughts and Outlook -- Acknowledgments -- References -- Chapter 5 Chemical Matter That Binds RNA -- 5.1 Introduction -- 5.2 Natural Ligands -- 5.2.1 Aminoglycosides -- 5.2.2 Tetracyclines -- 5.2.3 Macrolides -- 5.2.4 Native Riboswitch Ligands -- 5.3 Commercial Ligands -- 5.3.1 Industrial Libraries -- 5.3.2 Academic Libraries -- 5.4 Synthetic Ligands -- 5.4.1 Benzimidazoles and Purines -- 5.4.2 Naphthalenes, Quinolines, and Quinazolines -- 5.4.3 Oxazolidinones -- 5.4.4 Amilorides -- 5.4.5 Diphenyl Furan -- 5.4.6 Multivalent Ligands -- 5.5 Computational Tools for the Exploration of Chemical Space -- 5.5.1 Similarity Searches and Principal Component Analysis -- 5.5.2 Additional Machine‐Learning Tools -- 5.5.3 Structure‐Based Ligand Design -- 5.6 Case Studies in Examining and Expanding RNA‐Targeted Chemical Space -- 5.6.1 Using QSAR to Probe RNA‐Targeting Small‐Molecule Properties -- 5.6.2 Evaluating the Chemical Space of Natural, Synthetic, and Commercial Ligands -- 5.7 Conclusions and Outlook -- Acknowledgments -- References -- Chapter 6 MicroRNAs as Targets for Small‐Molecule Binders -- 6.1 Introduction -- 6.2 MicroRNAs -- 6.3 MicroRNAs Biogenesis -- 6.4 Targeting MicroRNAs with Small‐Molecule RNA Binders -- 6.4.1 Induction of miRNAs Expression: Tackling the Decrease of Tumor Suppressor miRNAs -- 6.4.2 Inhibition of miRNAs Production: Pre‐ and Pri‐miRNA Binders -- 6.4.2.1 Discovery of miRNAs Inhibitors by Intracellular Assays -- 6.4.2.2 Target‐Based In Vitro Assays. 6.4.2.3 Design of Specific Ligands of Pre‐ and Pri‐miRNAs -- 6.4.2.4 Fragment‐Based Drug Design -- 6.4.2.5 DNA‐Encoded Libraries (DELs) -- 6.5 Inhibition of RNA-Protein Interactions in miRNAs Pathways -- 6.6 Adding Cleavage Properties to miRNAs Interfering Agents -- 6.7 Conclusions -- References -- Chapter 7 Pre‐mRNA Splicing Modulation -- 7.1 Introduction -- 7.2 Overview of Splicing Biology -- 7.2.1 The Spliceosome -- 7.2.2 Classes of Alternative Splicing -- 7.3 Pharmacological Mechanisms of Splicing Modulation -- 7.3.1 Cis‐ and Trans‐Regulatory Elements (Splicing Factors) -- 7.3.1.1 Stabilization of Cis‐Regulatory Elements -- 7.3.1.2 Destabilization of Cis‐Regulatory Elements -- 7.3.1.3 Inhibition of Cis‐Regulatory RNA-Protein Interactions -- 7.3.1.4 Inhibition of Trans‐Regulatory Elements -- 7.3.1.5 Degradation of Trans‐Regulatory Elements -- 7.3.1.6 Inhibition of Trans‐Regulatory Element Protein-Protein Interactions (PPIs) -- 7.3.1.7 Stabilization of Trans‐Regulatory Element RNA-Protein Interactions (RPIs) -- 7.3.2 Kinases and Phosphatases -- 7.3.2.1 Challenges in Targeting Kinases -- 7.3.2.2 Inhibition of Kinases -- 7.3.2.3 Activation and Degradation of Kinases -- 7.3.2.4 Inhibition and Activation of Protein Phosphatases -- 7.3.3 Epigenetic Writers and Erasers -- 7.3.3.1 Inhibition of Epigenetic Writers -- 7.3.4 RNA Helicases -- 7.3.5 Drugging the Spliceosome -- 7.3.5.1 Inhibition of U2 snRNP Recognition of the 3′‐Splice Site -- 7.3.5.2 E7107 -- 7.3.5.3 H3B‐8800 -- 7.3.5.4 Stabilizers of U1 snRNP Recognition of the 5′‐Splice Site -- 7.3.5.5 Introduction to Spinal Muscular Atrophy (SMA) -- 7.3.5.6 Risdiplam (Evrysdi®) -- 7.4 Future Outlook -- References -- Chapter 8 Prospects for Riboswitches in Drug Development -- 8.1 Introduction -- 8.1.1 The Known Landscape of Riboswitches -- 8.1.2 Riboswitches in Drug Development. 8.1.3 The Need for Novel Antibiotics -- 8.2 Riboswitches as Drug Targets -- 8.2.1 Why Target Riboswitches? -- 8.2.2 Features of a Druggable Riboswitch -- 8.2.3 Riboswitch‐Targeted Drugs -- 8.2.3.1 Small Molecules Targeting FMN Riboswitches -- 8.2.3.2 Other Riboswitches Targeted in Proof‐of‐Principle Demonstrations -- 8.2.4 Barriers and Future Developments -- 8.3 Riboswitches as Tools for Antibiotic Drug Development -- 8.3.1 Riboswitches as Biosensors -- 8.3.2 A Riboswitch‐Based Fluoride Sensor Illuminates Agonists of Fluoride Toxicity -- 8.3.3 A Riboswitch‐Based ZTP Sensor Identifies Inhibitors of Folate Biosynthesis -- 8.3.4 A Riboswitch‐Based SAH Sensor Reveals an Inhibitor of SAH Nucleosidase -- 8.3.5 Barriers and Future Developments -- 8.4 Application of Riboswitches in Gene Therapy -- 8.4.1 Considerations for Designer Riboswitches -- 8.4.2 Eukaryotic Expression Platforms -- 8.4.3 Barriers and Future Developments -- 8.5 Concluding Remarks -- Acknowledgment -- References -- Chapter 9 Small Molecules That Degrade RNA -- 9.1 Antisense Oligonucleotide Degraders -- 9.2 Small‐Molecule Direct Degraders -- 9.2.1 N‐Hydroxypyridine‐2(1H)‐thione (N‐HPT) Conjugates -- 9.2.2 Bleomycin -- 9.2.3 Bleomycin Conjugates -- 9.2.3.1 Bleomycin Degraders Targeting the r(CUG) Repeat Expansion That Causes DM1 -- 9.2.3.2 Bleomycin Degraders Targeting r(CCUG) Repeat Expansion that Causes DM2 -- 9.2.3.3 Bleomycin Degraders Targeting Oncogenic Precursor microRNAs -- 9.2.3.4 Conclusions and Outlook for Bleomycin‐Based Direct Degraders -- 9.3 Ribonuclease Targeting Chimeras (RiboTACs) -- 9.3.1 RNase L is an Endogenous Endoribonuclease That Functions as Part of the Innate Immune Response -- 9.3.2 First‐Generation RiboTACs Targeting Oncogenic miRNAs -- 9.3.3 Small‐Molecule‐Based RiboTACs -- 9.3.4 Comparison of Bleomycin‐Based Direct Degraders and RiboTACs. 9.3.5 Discovery of Additional Small‐Molecule RNase L Activators -- 9.3.6 Conclusions and Outlook for RiboTACs -- 9.4 Summary and Outlook for Small‐Molecule RNA Degraders -- References -- Chapter 10 Approaches to the Identification of Molecules Altering Programmed Ribosomal Frameshifting in Viruses -- 10.1 Introduction -- 10.2 Mechanisms of Frameshifting -- 10.3 Targeting Frameshifting in HIV -- 10.4 Targeting Frameshifting in SARS‐CoV‐1 and SARS‐CoV‐2 -- 10.5 Conclusions -- References -- Chapter 11 RNA-Protein Interactions: A New Approach for Drugging RNA Biology -- 11.1 Molecular Basis of RNA-Protein Interactions -- 11.1.1 RNA Recognition Motifs (RRMs) -- 11.1.2 Double‐Stranded RNA‐Binding Domains (dsRBD) -- 11.1.3 Zinc Finger (ZnF) Domains -- 11.1.4 K Homology (KH) Domains -- 11.1.5 Other RBDs -- 11.2 Regulation and Dysregulation of RNA-Protein Interactions -- 11.2.1 Poor Quality Control Leads to Over‐ and Underproduction of RBPs -- 11.2.2 RBPs Become Out of Control, mRNA Processing Gets a Makeover (and Hates It) -- 11.2.3 RBP Shuttling of mRNA Becomes Askew -- 11.2.4 The RBP is Lost and Wreaks Havoc on the Cell -- 11.2.5 RBPs Dictate Which mRNAs are Translated, Favoring their Toxic Friends -- 11.2.6 RBPs and RNA Become Very Clique‐y, Form Their Own Complex and Cause Stress to the Rest of the Cell -- 11.3 Experimental Methods to Detect and Screen for Small Molecules that Modulate RNA-Protein Interactions -- 11.3.1 In vitro Fluorescence‐Based Assays -- 11.3.2 In vitro Chemiluminescence‐Based Assays -- 11.3.2.1 Cell‐Based RPI Detection Assays -- 11.3.3 Cell‐Based RNA-Protein Interaction Screening -- 11.4 Closing Remarks -- References -- Chapter 12 Drugging the Epitranscriptome -- 12.1 Introduction -- 12.2 Modifications on mRNA: N6‐Methyladenosine, Pseudouridine, and Inosine -- 12.2.1 N6‐Methyladenosine (m6A) -- 12.2.2 Pseudouridine (Ψ). 12.2.3 Inosine (I). |
| Record Nr. | UNINA-9910877076603321 |
|
Schneekloth John
|
||
| Newark : , : John Wiley & Sons, Incorporated, , 2024 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Thermodynamics and kinetics of drug binding / / edited by György M. Keserü and David C. Swinney
| Thermodynamics and kinetics of drug binding / / edited by György M. Keserü and David C. Swinney |
| Pubbl/distr/stampa | Weinheim, Germany : , : Wiley-VCH Verlag, , 2015 |
| Descrizione fisica | 1 online resource (765 p.) |
| Disciplina | 615.7 |
| Collana | Methods and Principles in Medicinal Chemistry |
| Soggetto topico |
Binding sites (Biochemistry) - Thermodynamics
Pharmacokinetics |
| ISBN |
3-527-67302-4
3-527-67304-0 3-527-67305-9 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto |
Cover; Series; Title Page; Copyright; List of Contributors; Preface; A Personal Foreword; Section I; Chapter 1: The Binding Thermodynamics of Drug Candidates; 1.1 Affinity Optimization; 1.2 The Binding Affinity; 1.3 The Enthalpy Change; 1.4 The Entropy Change; 1.5 Engineering Binding Contributions; 1.6 Lipophilic Efficiency and Binding Enthalpy; Acknowledgments; References; Chapter 2: van't Hoff Based Thermodynamics; 2.1 Relevance of Thermodynamics to Pharmacology; 2.2 Affinity Constant Determination; 2.3 The Origin of van't Hoff Equation
2.4 From van't Hoff toward Thermodynamic Discrimination2.5 Representation of ΔG°, ΔH°, and ΔS° Data; 2.6 The Adenosine Receptors Binding Thermodynamics Story; 2.7 Binding Thermodynamics of G-Protein Coupled Receptors; 2.8 Binding Thermodynamics of Ligand-Gated Ion Channel Receptors; 2.9 Discussion; Abbreviations; References; Chapter 3: Computation of Drug-Binding Thermodynamics; 3.1 Introduction; 3.2 Potential of Mean Force Calculations; 3.3 Alchemical Transformations; 3.4 Nonequilibrium Methods; 3.5 MM-PBSA; 3.6 Linear Interaction Energy; 3.7 Scoring Functions; 3.8 Free-energy Components 3.9 SummaryReferences; Chapter 4: Thermodynamics-Guided Optimizations in Medicinal Chemistry; 4.1 Introduction; 4.2 The Thermodynamics of Medicinal Chemistry Optimizations; 4.3 Selection of Suitable Starting Points; 4.4 Thermodynamics Based Optimization Strategies; References; Chapter 5: From Molecular Understanding to Structure-Thermodynamic Relationships, the Case of Acetylcholine Binding Proteins; 5.1 Introduction; 5.2 Acetylcholine Binding Proteins (AChBPs); 5.3 Thermodynamics of Small Molecule Binding at AChBPs; 5.4 Concluding Remarks and Outlook; References Chapter 6: Thermodynamics in Lead Optimization6.1 Introduction to Lead Optimization in Drug Discovery; 6.2 Measurement of Thermodynamic Parameters in Lead Optimization; 6.3 Advantages during Lead Optimization for Thermodynamic Measurements; 6.4 Exploitation of Measured Thermodynamics in Lead Optimization; 6.5 Lead Optimization beyond Affinity; 6.6 Exemplary Case Studies; 6.7 Potential Complicating Factors in Exploiting Thermodynamics in Lead Optimization; 6.8 Summary; References; Chapter 7: Thermodynamic Profiling of Carbonic Anhydrase Inhibitors; 7.1 Introduction 7.2 Thermodynamic Profiles of Fragment Inhibitors7.3 Thermodynamics of Fragment Growing; 7.4 Conclusions; Acknowledgments; References; Section II; Chapter 8: Drug-Target Residence Time; 8.1 Introduction; 8.2 Open and Closed Systems in Biology; 8.3 Mechanisms of Drug-Target Interactions; 8.4 Impact of Residence Time on Cellular Activity; 8.5 Impact on Efficacy and Duration In vivo; 8.6 Limitations of Drug-Target Residence Time; 8.7 Summary; References; Chapter 9: Experimental Methods to Determine Binding Kinetics; 9.1 Introduction; 9.2 Definitions; 9.3 Experimental Strategy 9.4 Experimental Methodologies |
| Record Nr. | UNINA-9910131450303321 |
| Weinheim, Germany : , : Wiley-VCH Verlag, , 2015 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Thermodynamics and kinetics of drug binding / / edited by György M. Keserü and David C. Swinney
| Thermodynamics and kinetics of drug binding / / edited by György M. Keserü and David C. Swinney |
| Pubbl/distr/stampa | Weinheim, Germany : , : Wiley-VCH Verlag, , 2015 |
| Descrizione fisica | 1 online resource (765 p.) |
| Disciplina | 615.7 |
| Collana | Methods and Principles in Medicinal Chemistry |
| Soggetto topico |
Binding sites (Biochemistry) - Thermodynamics
Pharmacokinetics |
| ISBN |
3-527-67302-4
3-527-67304-0 3-527-67305-9 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto |
Cover; Series; Title Page; Copyright; List of Contributors; Preface; A Personal Foreword; Section I; Chapter 1: The Binding Thermodynamics of Drug Candidates; 1.1 Affinity Optimization; 1.2 The Binding Affinity; 1.3 The Enthalpy Change; 1.4 The Entropy Change; 1.5 Engineering Binding Contributions; 1.6 Lipophilic Efficiency and Binding Enthalpy; Acknowledgments; References; Chapter 2: van't Hoff Based Thermodynamics; 2.1 Relevance of Thermodynamics to Pharmacology; 2.2 Affinity Constant Determination; 2.3 The Origin of van't Hoff Equation
2.4 From van't Hoff toward Thermodynamic Discrimination2.5 Representation of ΔG°, ΔH°, and ΔS° Data; 2.6 The Adenosine Receptors Binding Thermodynamics Story; 2.7 Binding Thermodynamics of G-Protein Coupled Receptors; 2.8 Binding Thermodynamics of Ligand-Gated Ion Channel Receptors; 2.9 Discussion; Abbreviations; References; Chapter 3: Computation of Drug-Binding Thermodynamics; 3.1 Introduction; 3.2 Potential of Mean Force Calculations; 3.3 Alchemical Transformations; 3.4 Nonequilibrium Methods; 3.5 MM-PBSA; 3.6 Linear Interaction Energy; 3.7 Scoring Functions; 3.8 Free-energy Components 3.9 SummaryReferences; Chapter 4: Thermodynamics-Guided Optimizations in Medicinal Chemistry; 4.1 Introduction; 4.2 The Thermodynamics of Medicinal Chemistry Optimizations; 4.3 Selection of Suitable Starting Points; 4.4 Thermodynamics Based Optimization Strategies; References; Chapter 5: From Molecular Understanding to Structure-Thermodynamic Relationships, the Case of Acetylcholine Binding Proteins; 5.1 Introduction; 5.2 Acetylcholine Binding Proteins (AChBPs); 5.3 Thermodynamics of Small Molecule Binding at AChBPs; 5.4 Concluding Remarks and Outlook; References Chapter 6: Thermodynamics in Lead Optimization6.1 Introduction to Lead Optimization in Drug Discovery; 6.2 Measurement of Thermodynamic Parameters in Lead Optimization; 6.3 Advantages during Lead Optimization for Thermodynamic Measurements; 6.4 Exploitation of Measured Thermodynamics in Lead Optimization; 6.5 Lead Optimization beyond Affinity; 6.6 Exemplary Case Studies; 6.7 Potential Complicating Factors in Exploiting Thermodynamics in Lead Optimization; 6.8 Summary; References; Chapter 7: Thermodynamic Profiling of Carbonic Anhydrase Inhibitors; 7.1 Introduction 7.2 Thermodynamic Profiles of Fragment Inhibitors7.3 Thermodynamics of Fragment Growing; 7.4 Conclusions; Acknowledgments; References; Section II; Chapter 8: Drug-Target Residence Time; 8.1 Introduction; 8.2 Open and Closed Systems in Biology; 8.3 Mechanisms of Drug-Target Interactions; 8.4 Impact of Residence Time on Cellular Activity; 8.5 Impact on Efficacy and Duration In vivo; 8.6 Limitations of Drug-Target Residence Time; 8.7 Summary; References; Chapter 9: Experimental Methods to Determine Binding Kinetics; 9.1 Introduction; 9.2 Definitions; 9.3 Experimental Strategy 9.4 Experimental Methodologies |
| Record Nr. | UNINA-9910830179403321 |
| Weinheim, Germany : , : Wiley-VCH Verlag, , 2015 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
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