Details

Molecular Technology


Molecular Technology

Life Innovation
1. Aufl.

von: Hisashi Yamamoto, Takashi Kato

124,99 €

Verlag: Wiley-VCH
Format: PDF
Veröffentl.: 03.08.2018
ISBN/EAN: 9783527802760
Sprache: englisch
Anzahl Seiten: 400

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Beschreibungen

Edited by foremost leaders in chemical research together with a number of distinguished international authors, Volume 2 presents the most important and promising recent chemical developments in life sciences, neatly summarized in one book. Interdisciplinary and application-oriented, this ready reference focuses on methods and processes with a high practical aspect, covering new trends in drug delivery, in-vivo analysis, structure formation and much more.Of great interest to chemists and life scientists in academia and industry.
Foreword by Dr Hamaguchi xiii Foreword by Dr Noyori xv Preface xvii 1 Control of DNA Packaging by Block Catiomers for Systemic Gene Delivery System 1Kensuke Osada 1.1 Introduction 1 1.2 Packaging of pDNA by Block Catiomers 2 1.2.1 Rod-Shaped Packaging of pDNA 3 1.2.2 Rod Shape or Globular Shape 5 1.3 PolyplexMicelles as a Systemic Gene Delivery System 6 1.3.1 Stable Encapsulation of pDNAWithin Polyplex Micelles for Systemic Delivery 6 1.3.2 PolyplexMicelles for Efficient Cellular Entry 9 1.3.3 PolyplexMicelles for Safe Endosome Escape 11 1.3.4 PolyplexMicelles for Nuclear Translocation 13 1.3.5 PolyplexMicelles for Efficient Transcription 13 1.4 Design Criteria of Block Catiomers Toward Systemic Gene Therapy 14 1.5 Rod Shape or Toroid Shape 17 1.6 Summary 18 References 18 2 Manipulation of Molecular Architecture with DNA 25Akinori Kuzuya 2.1 Introduction 25 2.2 Molecular Structure of DNA 25 2.3 Immobile DNA Junctions 26 2.4 Topologically Unique DNA Molecules 28 2.5 DNA Tiles and Their Assemblies 28 2.6 DNA Origami 30 2.7 DNA Origami as a Molecular Peg Board 32 2.8 Molecular Machines Made of DNA Origami 33 2.9 DNA Origami Pinching Devices 33 2.10 Novel Design Principles 35 2.11 DNA-PAINT: An Application of DNA Devices 36 2.12 Prospects 36 References 36 3 Chemical Assembly Lines for Skeletally Diverse Indole Alkaloids 43Hiroki Oguri 3.1 Introduction 43 3.2 Macmillan’s Collective Total Synthesis by Means of Organocascade Catalysis 45 3.3 Systematic Synthesis of Indole Alkaloids Employing Cyclopentene Intermediates by the Zhu Group 52 3.4 Biogenetically Inspired Synthesis Employing a Multipotent Intermediate by the Oguri Group 58 References 68 4 Molecular Technology for Injured Brain Regeneration 71Itsuki Ajioka 4.1 Introduction 71 4.2 Biology of Angiogenesis 71 4.3 Angiogenesis for Injured Brain Regeneration 73 4.4 Molecular Technology to Promote Angiogenesis 74 4.5 Biology of Cell Cycle 75 4.6 Biology of Neurogenesis 77 4.7 Molecular Technology to Promote Neuron Regeneration 78 4.8 Conclusion 80 References 80 5 Engineering the Ribosomal Translation Systemto Introduce Non-proteinogenic Amino Acids into Peptides 87Takayuki Katoh 5.1 Introduction 87 5.2 Decoding the Genetic Code 88 5.3 Aminoacylation of tRNA by Aminoacyl-tRNA Synthetases 90 5.4 Methods for Preparing Noncanonical Aminoacyl-tRNAs 91 5.4.1 Ligation of Aminoacyl-pdCpA Dinucleotide with tRNA Lacking the 3?-Terminal CA 91 5.4.2 Post-aminoacylationModification of Aminoacyl-tRNA 93 5.4.3 Misacylation of Non-proteinogenic Amino Acids by ARSs 94 5.4.4 Flexizyme, an Aminoacylation Ribozyme 94 5.5 Methods for Assigning Non-proteinogenic Amino Acids to the Genetic Code 95 5.5.1 The Nonsense Codon Method 96 5.5.2 Genetic Code Reprogramming 97 5.5.3 The Four-base Codon Method 98 5.5.4 The Nonstandard Base Method 100 5.6 Limitation of the Incorporation of Noncanonical Amino Acids: Substrate Scope 101 5.7 Improvement of the Substrate Tolerance of Ribosomal Translation 103 5.8 Ribosomally Synthesized Noncanonical Peptides as Drug Discovery Platforms 104 5.9 Summary and Outlook 105 References 106 6 Development of Functional Nanoparticles and Their Systems Capable of Accumulating to Tumors 113Satoru Karasawa 6.1 Introduction 113 6.2 Accumulation Based on Aberrant Morphology and Size 114 6.3 Accumulation Based on Aberrant pH Microenvironment 117 6.4 Accumulation Based on Temperature of Tumor Microenvironment 124 6.5 Perspective 129 References 129 7 Glycan Molecular Technology for Highly Selective In Vivo Recognition 131Katsunori Tanaka 7.1 Molecular Technology for Chemical Glycan Conjugation 133 7.1.1 Conjugation to Lysine 133 7.1.2 Conjugation to Cysteine 133 7.1.3 Bioorthogonal Conjugation 136 7.1.4 Enzymatic Glycosylation 136 7.2 In Vivo Kinetic Studies of Monosaccharide-Modified Proteins 137 7.2.1 Dissection-Based Kinetic and Biodistribution Studies: Effects of Protein Modification by Galactose, Mannose, and Fucose 137 7.2.2 Noninvasive Imaging of In Vivo Kinetic and Organ-Specific Accumulation of Monosaccharide-Modified Proteins 138 7.3 In Vivo Kinetic Studies of Oligosaccharide-Modified Proteins 139 7.3.1 In Vivo Kinetics of Proteins Modified by a Few Molecules of N-glycans 139 7.3.2 In Vivo Kinetics of Proteins Modified by Many N-glycans: Homogeneous N-glycoalbumins 141 7.3.3 In Vivo Kinetics of Proteins Modified by Many N-glycans: Heterogeneous N-glycoalbumins 145 7.3.4 Tumor Targeting by N-glycoalbumins 148 7.3.5 Glycan Molecular Technology on Live Cells: Tumor Targeting by N-glycan-Engineered Lymphocytes 148 7.4 Glycan Molecular Technology Adapted as Metal Carriers: In Vivo Metal-Catalyzed Reactions within Live Animals 150 7.5 Concluding Remarks 153 Acknowledgments 155 References 155 8 Molecular Technology Toward Expansion of Nucleic Acid Functionality 165Michiko Kimoto and Kiyohiko Kawai 8.1 Introduction 165 8.2 Molecular Technologies that Enable Genetic Alphabet Expansion 168 8.2.1 Nucleotide Modification 168 8.2.2 Unnatural Base Pairs (UBPs) asThird Base Pairs Toward Expansion of Nucleic Acid Functionality 168 8.2.3 High-Affinity DNA Aptamer Generation Using the Expanded Genetic Alphabet 169 8.3 Molecular Technologies that Enable Fluorescence Blinking Control 171 8.3.1 Single Molecule Detection Based on Blinking Observations 171 8.3.2 Blinking Kinetics 172 8.3.3 Control of Fluorescence Blinking by DNA Structure 174 8.3.3.1 Triplet Blinking 174 8.3.3.2 Redox Blinking 175 8.3.3.3 Isomerization Blinking 176 8.4 Conclusions 178 Acknowledgments 178 References 178 9 Molecular Technology for Membrane Functionalization 183MichioMurakoshi and TakahiroMuraoka 9.1 Introduction 183 9.2 Synthetic Approach for Membrane Functionalization 185 9.2.1 Formation of Multipass Transmembrane Structure 185 9.2.2 Formation of Supramolecular Ion Channels 187 9.2.3 Demonstration of Ligand-Gated Ion Transportation 187 9.2.4 Light-Triggered Membrane Budding 190 9.3 Semi-biological Approach for Membrane Functionalization 191 9.3.1 Mechanical Analysis of the Transmembrane Structure of Membrane Proteins 191 9.3.2 Development of the Nanobiodevice Using a Membrane Protein Expressing in the Inner Ear 193 9.3.3 Improvement of Protein Performance by Genetic Engineering 198 References 199 10 Molecular Technology for Degradable Synthetic Hydrogels for Biomaterials 203Hiroharu Ajiro and Takamasa Sakai Scope of the Chapter 203 10.1 Degradation Behavior of Hydrogels 203 10.2 Polylactide Copolymer 205 10.3 Trimethylene Carbonate Derivatives 207 10.4 Polyurethane 211 References 213 11 Molecular Technology for Epigenetics Toward Drug Discovery 219Takayoshi Suzuki 11.1 Introduction 219 11.2 Epigenetics 219 11.3 Isozyme-Selective Histone Deacetylase (HDAC) Inhibitors 221 11.3.1 Identification of HDAC3-Selective Inhibitors by Click Chemistry Approach 221 11.3.2 Identification of HDAC8-Selective Inhibitors by Click Chemistry Approach and Structure-Based Drug Design 224 11.3.3 Identification of HDAC6-Insensitive Inhibitors Using C–H Activation Reaction 224 11.3.4 Identification of HDAC6-Selective Inhibitors by Substrate-Based Drug Design 228 11.3.5 Identification of SIRT1-Selective Inhibitors by Target-Guided Synthesis 228 11.3.6 Identification of SIRT2-Selective Inhibitors by Structure-Based Drug Design and Click Chemistry Approach 232 11.4 Histone Lysine Demethylase (KDM) Inhibitors 234 11.4.1 Identification of KDM4C Inhibitors by Structure-Based Drug Design 235 11.4.2 Identification of KDM5A Inhibitors by Structure-Based Drug Design 237 11.4.3 Identification of KDM7B Inhibitors by Structure-Based Drug Design 238 11.4.4 Identification of LSD1 Inhibitors by Target-Guided Synthesis 239 11.4.5 Small-Molecule-Based Drug Delivery System Using LSD1 and its Inhibitor 250 11.5 Summary 253 References 254 12 Molecular Technology for Highly Efficient Gene Silencing: DNA/RNA Heteroduplex Oligonucleotides 257Kotaro Yoshioka, Kazutaka Nishina, Tetsuya Nagata, and Takanori Yokota 12.1 Introduction 257 12.2 Therapeutic Oligonucleotides 257 12.2.1 siRNA 257 12.2.2 ASO 258 12.3 Chemical Modifications ofTherapeutic Oligonucleotide 259 12.3.1 Modifications of Internucleotide Linkage 259 12.3.2 Modifications of Sugar Moiety 260 12.4 Ligand Conjugation for DDS 261 12.4.1 Development of Ligand Molecules for Therapeutic Oligonucleotides 261 12.4.2 Vitamin E for Ligand Molecule 261 12.4.3 siRNA Conjugated with Tocopherol 261 12.4.4 ASO Conjugated with Tocopherol 261 12.5 DNA/RNA Heteroduplex Oligonucleotide 262 12.5.1 Basic Concept of Heteroduplex Oligonucleotide 262 12.5.2 HDO Conjugated with Tocopherol (Toc-HDO) 264 12.5.2.1 Design of Toc-HDO 264 12.5.2.2 Potency of Toc-HDO 264 12.5.2.3 Adverse Effect of Toc-HDO 266 12.5.2.4 Mechanism of Toc-HDO 268 12.6 Future Prospects 269 References 269 13 Molecular Technology for Highly Sensitive Biomolecular Analysis: Hyperpolarized NMR/MRI Probes 273Shinsuke Sando and Hiroshi Nonaka 13.1 Hyperpolarization 273 13.2 Requirements for HP Molecular Imaging Probes 275 13.3 HP 13C Molecular Probes for Analysis of Enzymatic Activity 277 13.3.1 [1-13C]Pyruvate 277 13.3.2 HP 13C Probes for Analysis of Glycolysis and Tricarboxylic Acid Cycle 278 13.3.3 ?-Glutamyl-[1-13C]glycine: HP 13C Probe for Analysis of ?-glutamyl Transpeptidase 278 13.3.4 [1-13C]Alanine-NH2: HP 13C Probes for Analysis of Aminopeptidase N 282 13.4 HP 13C Molecular Probes for Analysis of the Chemical Environment 283 13.4.1 [1-13C]Bicarbonate 283 13.4.2 [1-13C]Ascorbate and Dehydroascorbate 283 13.4.3 [13C]Benzoylformic Acid for Sensing H2O2 284 13.4.4 [13C,D3]-p-Anisidine for Sensing of HOCl 284 13.4.5 [13C,D]EDTA for Sensing of Metal Ions 285 13.5 HP 15N Molecular Probes 286 13.6 A Strategy for Designing HP Molecular Probes 287 13.6.1 Scaffold Structure for Design of 15NHP Probes: [15N,D9]TMPA 288 13.6.1.1 [15N,D14]TMPA 291 13.6.2 Scaffold Structure for Designing 13CHyperpolarized Probes 292 13.7 Conclusion 294 References 294 14 Molecular Technologies in Life Innovation: Novel Molecular Technologies for Labeling and Functional Control of Proteins Under Live Cell Conditions 297Itaru Hamachi, Shigeki Kiyonaka, Tomonori Tamura, and Ryou Kubota 14.1 General Introduction 297 14.2 Ligand-Directed Chemistry for Neurotransmitter Receptor Proteins Under Live Cell Condition and its Application 300 14.3 Affinity-Guided DMAP Reaction for Analysis of Live Cell Surface Proteins 308 14.4 Coordination Chemistry-Based Chemogenetic Approach to Switch the Activity of Glutamate Receptors in Live Cells 312 14.5 Concluding Remarks 320 References 321 15 Molecular Technologies for Pseudo-natural Peptide Synthesis and Discovery of Bioactive Compounds Against Undruggable Targets 329Joseph M. Rogers and Hiroaki Suga 15.1 Introduction 329 15.2 Peptides Could Target Undruggable Targets 330 15.2.1 Druggable Proteins 330 15.2.2 Undruggable Proteins 332 15.2.3 Natural Peptides as Drugs 333 15.2.4 Modification to Peptides can ImproveTheir Drug-Like Characteristics 334 15.2.4.1 Macrocyclization 334 15.2.4.2 Amino Acids with Unnatural Side Chains 335 15.2.4.3 Backbone Modifications Including N-Methylation 335 15.2.4.4 Cyclosporin – A Membrane-Permeable Anomaly 336 15.2.4.5 Membrane Permeability Cannot be Calculated from Amino Acid Content 336 15.2.5 Cyclosporin –The Inspiration for the Cyclic Peptide Approach to Undruggable Targets 337 15.3 Molecular Technologies to Discover Functional Peptides 337 15.3.1 Ribosomal Synthesis of Peptides 337 15.3.2 Natural Peptide Synthesis is an Efficient Method to Generate Huge Libraries 339 15.3.3 Selection Methods 340 15.3.3.1 Intracellular Peptide Selection 340 15.3.3.2 Phage Display 341 15.3.3.3 A Cell-Free Display, mRNA Display 345 15.3.4 Other Methods of Selection 347 15.4 Molecular Technology for Pseudo-natural Peptide Synthesis and Its Use in Peptide Drug Discovery 347 15.4.1 The Need for Pseudo-natural Synthesis –The Limitations of SPPS 348 15.4.2 Intein Cyclization and SICLOPPS 348 15.4.3 Post-translationModification 351 15.4.4 Genetic Code Expansion 352 15.4.5 Replacing Amino Acids in Translation 354 15.4.6 Genetic Code Reprogramming 355 15.4.6.1 Flexizymes 355 15.4.6.2 RaPID System 356 15.5 Conclusion 361 Acknowledgment 361 References 362 Index 371
Hisashi Yamamoto is Professor at the University of Chicago. He received his Ph.D. from Harvard under the mentorship of Professor E. J. Corey. His first academic position was as Assistant Professor and lecturer at Kyoto University, and in 1977 he was appointed Associate Professor of Chemistry at the University of Hawaii. In 1980 he moved to Nagoya University where he became Professor in 1983. In 2002, he moved to United States as Professor at the University of Chicago. He has been honored to receive the Prelog Medal in 1993, the Chemical Society of Japan Award in 1995, the National Prize of Purple Medal (Japan) in 2002, Yamada Prize in 2004, and Tetrahedron Prize in 2006 and the ACS Award for Creative Work in Synthetic Organic Chemistry to name a few. He authored more than 500 papers, 130 reviews and books (h-index ~90). Takashi Kato is a Professor at the Department of Chemistry and Biotechnology at the University of Tokyo since 2000. After his postdoctoral research at Cornell University, Department of Chemistry with Professor Jean M. J. Frechet, he joined the University of Tokyo. He is the recipient of The Chemical Society of Japan Award for Young Chemists (1993), The Wiley Polymer Science Award (Chemistry), the 17th IBM Japan Science Award (Chemistry), the 1st JSPS (Japan Society for the Promotion of Science) Prize and the Award of Japanese Liquid Crystal Society (2008). He is the editor in chief of the "Polymer Journal", and member of the editorial board of "New Journal of Chemistry".

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