| Description |
1 online resource (350 pages) |
| Series |
The Taylor & Francis series in pharmaceutical sciences |
|
Taylor & Francis series in pharmaceutical sciences.
|
| Contents |
Book Cover -- Title -- Copyright -- Contents -- Contributors -- Preface -- PART ONE General Features -- 1 Mechanisms of Action of Antisense Oligonucleotides -- 1.1 Introduction -- 1.2 Cell Proliferation Arrest through Release of Deoxynucleosides -- 1.3 Extracellular Aptameric Effects of Phosphorothioate Oligodeoxynucleotide Analogues -- 1.4 Aptameric Effects of G-quartet Oligonucleotides and Analogues -- 1.5 Immune Stimulation by Oligodeoxynucleotides Containing CpG Motifs -- 1.6 Other Activities of Oligodeoxynucleotides Containing CpG Motifs -- 1.7 Antisense Inhibition of Gene Expression by Steric Block -- 1.8 Antisense Inhibition of Gene Expression through Ribonuclease H-mediated Destruction of Target mRNA -- 1.9 Oligonucleotides in Vivo -- 1.10 Conclusions -- Acknowledgements -- References -- PART TWO Chemical Aspects -- 2 Chemistry of Oligonucleotides -- 2.1 Introduction -- 2.2 Design of Oligonucleotides -- 2.2.1 Design Criteria for Antisense, Ribozymes, Triplex -- 2.2.2 Degree of Modification -- 2.3 Oligonucleotide Modifications: Synthesis and Properties -- 2.3.1 Unmodified Oligonucleotides having 3 5 -Phosphodiester Linkages -- 2.3.1.1 Chemical synthesis -- 2.3.1.2 Enzymatic synthesis and ligation -- 2.3.2 Oligonucleotides with 2 5'-Linkages and 3'3'-/ 5'5'-Inversions -- 2.3.3 Modification on Phosphorus -- 2.3.3.1 Phosphorothioates -- 2.3.3.2 Alkylphosphonates and arylphosphonates -- 2.3.3.3 Other modifications on phosphorus -- 2.3.4 Oligonucleotides Containing Dephospho Linkages -- 2.3.5 Modification of the Sugar Moiety -- 2.3.5.1 Ü-Anomeric oligonucleotides -- 2.3.5.2 2 -Modified oligonucleotides -- 2.3.5.3 Sterically locked nucleic acid analogues -- 2.3.5.4 Other sugar-modified analogues -- 2.3.6 Peptide Nucleic Acids -- 2.3.7 Modification on Heterocyclic Bases -- 2.3.7.1 Universal bases and abasic sites |
|
2.3.8 Oligonucleotide conjugates -- 2.3.8.1 5 -end conjugates -- 2.3.8.2 3 -end conjugates -- 2.3.8.3 Conjugation at internucleoside linkages, nucleobases and ribose -- 2.3.8.4 Types of conjugate -- 2.4 Analysis of Oligonucleotides -- 2.4.1 UV Spectroscopy of Oligonucleotides -- 2.4.1.1 Quantification of oligonucleotides -- 2.41.2 Melting curves of DNA -- 2.4.2 Analysis of Oligonucleotides by High-Performance Liquid Chromatography -- 2.4.2.1 Reversed-phase HPLC -- 2.4.2.2 Anion-exchange HPLC -- 2.4.3 Electrophoretic Techniques -- 2.4.3.1 Polyacrylamide Gel Electrophoresis (PAGE) on slab gels -- 2.4.3.2 Capillary Gel Electrophoresis (CGE) -- 2.4.4 Mass Spectrometry of Oligonucleotides -- 2.4.4.1 Electrospray Ionization Mass Spectrometry (ESI-MS) -- 2.4.4.2 Matrix-Assisted Laser Desorption Ionization (MALDI) -- 2.4.5 NMR of Oligonucleotides -- 2.5 Conclusion -- Acknowledgement -- References -- 3 The Oligonucleoticle Prodrug Approach -- 3.1 Introduction -- 3.2 What Kind of Enzymolabile Group? -- 3.2.1 Structure -- 3.2.2 Mechanism of Hydrolysis -- 3.2.3 Dimers Stability in Biological Media -- 3.3 First Pro-oligonucleotide Models -- 3.3.1 Post-synthesis Alkylation -- 3.3.2 Pro-oligonucleotides Stability in Biological Media -- 3.3.3 Limitations -- 3.3.4 Conclusion -- 3.4 Pro-oligonucleotides of the Second Generation -- 3.4.1 Phosphorous Environment -- 3.4.2 Automated Synthesis on Solid Support -- 3.4.2.7 Solid Support -- 3.4.2.2 Phosphoramidite building blocks -- 3.4.2.3 Protecting groups on nucleobases -- 3.4.3 Fully SATE Pro-oligonucleotides -- 3.4.4 Mixed Phosphodiester and SATE Phosphotriester Pro-oligonucleotides -- 3.4.5 Stability of Pro-oligonucleotides of Second Generation in Biological Media -- 3.4.6 Preliminary Data of Pro-oligos Cell Uptake -- 3.5 Conclusion -- Acknowledgements -- References -- 4 Peptide Nucleic Acids -- 4.1 Introduction |
|
4.2 Antisense -- 4.3 Antimicrobials -- 4.4 Anti-telomerase -- 4.5 Antigene -- 4.6 Anti-HIV -- 4.7 Pharmacology -- 4.8 Further Developments -- Acknowledgement -- References -- PART THREE Delivery -- 5 Peptide-mediated Delivery of Oligonucleotides -- 5.1 Delivery Vehicles for the Improved Uptake of Nucleic Acids: a Survey -- 5.2 The Potential of Peptides for Nucleic Acids Delivery -- 5.3 Strategies for the Coupling of Peptides to Oligonucleotides -- 5.4 Poly (L-lysine)-based Delivery Systems -- 5.5 Conjugation to Fusogenic Peptides Allowing Membrane Fusion or Membrane Translocation -- 5.5.1 Influenza Virus Haemagglutinin Fusogenic Peptide -- 5.5.2 HIV-1 gp41 Fusogenic Peptide -- 5.5.3 Antennapaedia Peptide -- 5.5.4 Tat Basic Domain -- 5.6 Conclusions -- Acknowledgements -- References -- 6 Polymeric Nanoparticles and Microparticles as Carriers for Antisense Oligonucleotides -- 6.1 Introduction -- 6.2 Nanoparticles -- 6.2.1 Rationale of Using Nanoparticles for the Delivery of ONs -- 6.2.2 Preparation of Nanoparticles by Polymerization of a Monomer -- 6.2.3 Nanoparticles Obtained from Preformed Polymers -- 6.2.4 Association of ONs to Nanoparticles -- 6.3 In Vitro Stability of ONs Adsorbed onto Nanoparticles -- 6.4 Cell Interactions with ON Loaded Nanoparticles -- 6.5 In Vitro Pharmacological Activity of Oligonucleotide-loaded Nanoparticles -- 6.6 In Vivo Studies with Oligonucleotide Nanoparticles -- 6.7 Microparticles -- 6.8 Conclusion -- References -- 7 Liposomes for the Delivery of Oligonucleotides -- 7.1 Introduction -- 7.2 Anionic Liposomes -- 7.3 Cationic Liposomes -- 7.3.1 Intracellular delivery and Distribution -- 7.3.2 Pharmacological Efficacy in Vitro -- 7.3.3 Pharmacological Efficacy in Vivo -- 7.4 pH-sensitive Liposomes -- 7.5 Immunoliposomes and Other Molecularly Targeted Liposomes -- 7.6 Fusogenic Liposomes and Proteoliposomes |
|
7.7 Conclusions -- References -- 8 Comb-type Polycation Copolymer for Antigène Strategy and DNA Carrier -- 8.1 Introduction -- 8.2 Comb-type Polycations as a Stabilizer for DNA Duplex and Triplex -- NA Carrier ... -- Acknowledgements -- References -- PART FOUR Biopharmaceutics -- 9 Delivery of Antisense Oligonucleotides in Vitro -- 9.1 Introduction -- 9.2 Oligonucleotide-Binding Proteins on the Cell Surface -- 9.3 Intracellular Compartmentalization -- 9.4 Oligonucleotide Delivery Reagents-Practical Considerations -- 9.5 Experimental Antisense: Points to Consider -- 9.5.1 Oligonucleotides -- 9.5.2 Delivery -- 9.5.3 Controls -- 9.5.4 Traps -- References -- 10 Mechanisms of Transmembrane Transport of Oligonucleotides -- 10.1 Overview of Cellular Uptake of Antisense Oligonucleotides -- 10.2 Permeation of Oligonucleotides across Membranes -- 10.2.1 Interactions of Oligonucleotides with the Lipid Bilayer -- 10.2.2 Oligonucleotide Receptors and Transporter Proteins -- 10.3 Mechanisms of Enhancement of Oligonucleotide Permeation across Membranes -- 10.4 Summary -- References -- 11 Pharmacokinetics of Oligodeoxynucleotides -- 11.1 Introduction -- 11.2 Pharmacokinetics -- 11.2.1 Analytical Chemistry -- 11.2.2 Stability -- 11.3 Chemistry of Oligonucleotides and Formulations -- 11.4 Cellular Pharmacokinetics -- 11.5 Preclinical Pharmacokinetics -- 11.6 Clinical Pharmacokinetics -- 11.7 Conclusions -- References -- PART FIVE Pharmacological Activity -- 12 Antisense as a Novel Therapy for Cancer -- 12.1 Novel Approaches for Anticancer Therapy -- 12.2 Antisense Approaches for Cancer -- 12.2.1 Bcl-2 -- 12.2.2 C-myb -- 12.2.3 raf Kinase -- 12.2.4 Protein Kinase C-Ü -- 12.2.5 Protein Kinase A -- 12.3 Antisense as a Novel Anticancer Approach against ras -- 12.3.1 Discovery of ras Antisense Inhibitors -- 12.3.2 Specificity of ras Antisense Inhibitors |
|
12.3.3 Cellular Responses Resulting from Inhibition of ras Gene Expression -- 12.3.4 Antitumour Activity of ras Antisense Oligonucleotides in Animal Models -- 12.4 Conclusions and Future Prospects -- Acknowledgements -- References -- 13 Modulation of Inflammatory Processes with Antisense Oligonucleoticles -- 13.1 Introduction -- 13.2 ICAM-1, a Case Study -- 13.2.1 Pharmacology of ICAM-1 Antisense Oligonucleotides -- 13.2.1.1 Proof of mechanism -- 13.2.1.2 Human xenografts -- 13.2.13 Rodent allografts -- 13.2.1.4 Renal ischaemia -- 73.2.7.5 Colitis -- 13.2.2 Toxicology of ICAM-1 Antisense Oligonucleotides -- 13.2.3 Clinical Studies with ISIS 2302 -- 13.2.4 Second- and Third-generation Chemistry -- 13.3 Other Examples -- 13.3.1 Other Endothelial-Leukocyte Adhesion Molecules -- 13.3.2 Interleukin 1 Receptor -- 13.3.3 NF-mB -- 13.3.4 Adenosine Receptors -- 13.3.5 Nitric Oxide Synthetase -- 13.4 Regulation of Immune Response by Non-antisense Mechanisms -- 13.5 Conclusions -- References -- 14 Oligonucleotides as Antiparasite Compounds -- 14.1 Introduction -- 14.2 Design of Antisense Oligonucleotides for Antiparasite Use -- 14.3 Antiparasite Effects of Antisense Oligonucleotides -- 14.3.1 Antisense Oligonucleotides against Plasmodium -- 14.3.2 Antisense Oligonucleotides against Trypanosomatids -- 14.3.3 Other Parasites -- 14.4 RNA Structures are Valid Targets for Regulatory Oligonucleotides -- 14.5 Conclusion -- Acknowledgements -- References -- Index |
| Summary |
Oligonucleotides diffuse poorly through biological barriers, including cell membranes. They are also rapidly degraded in vivo by nucleuses. Aiming to improve the administration of compounds, the book studies the development of nucleotide chemistry |
| Notes |
Publisher supplied metadata and other sources |
| Subject |
Nucleotides -- Therapeutic use
|
|
Oligonucleotides -- Therapeutic use
|
|
Oligonucleotides -- therapeutic use
|
|
Oligonucleotides -- adverse effects
|
|
Oligonucleotides -- Therapeutic use
|
|
Oligonucléotides -- usage thérapeutique.
|
|
Oligonucléotides -- effets indésirables.
|
|
Oligonucleotide
|
|
Anwendung
|
|
Therapie
|
|
Oligonucleotiden.
|
|
Farmacologie.
|
|
Acides nucléiques antisens -- Emploi en thérapeutique.
|
|
Vecteurs de médicaments.
|
| Form |
Electronic book
|
| Author |
Malvy, Claude
|
| ISBN |
9780203305669 |
|
0203305663 |
|
9781482268089 |
|
1482268086 |
|
