Abstract
As first-generation antisense oligonucleotides, more than a dozen phosphorothioate oligodeoxynucleotides (PS ODNs) have been clinically developed, but only one has reached the market. To improve the drawbacks of PS ODNs, such as low affinity to target mRNA and non-specific binding to proteins, modified oligonucleotides with 2-modified sugars such as 2-O-(2-methoxy)ethyl and 2-F modification or with bridged sugars such as oxyalkylene linkages between 2-oxygen and 4-carbon, have been synthesized as 2-MOE, 2-F RNA, 2,4-BNA/LNA and ENA oligonucleotides. They have shown properties of higher affinity to complementary single-stranded RNA and DNA than those of PS ODNs due to their preorganized N-conformation. On the basis of the properties of these newly designed oligonucleotides, their in vitro and in vivo applications for gene silencing as true antisense oligonucleotides have been reported. In this review, antisense applications with these modified oligonucleotides are focused on.
Keywords: DNA oligonucleotides, bridged nucleosides, Gapmers, Duchenne muscular dystrophy, RNA polymerase II
Current Topics in Medicinal Chemistry
Title: True Antisense Oligonucleotides with Modified Nucleotides Restricted in the Nconformation
Volume: 7 Issue: 7
Author(s): Makoto Koizumi
Affiliation:
Keywords: DNA oligonucleotides, bridged nucleosides, Gapmers, Duchenne muscular dystrophy, RNA polymerase II
Abstract: As first-generation antisense oligonucleotides, more than a dozen phosphorothioate oligodeoxynucleotides (PS ODNs) have been clinically developed, but only one has reached the market. To improve the drawbacks of PS ODNs, such as low affinity to target mRNA and non-specific binding to proteins, modified oligonucleotides with 2-modified sugars such as 2-O-(2-methoxy)ethyl and 2-F modification or with bridged sugars such as oxyalkylene linkages between 2-oxygen and 4-carbon, have been synthesized as 2-MOE, 2-F RNA, 2,4-BNA/LNA and ENA oligonucleotides. They have shown properties of higher affinity to complementary single-stranded RNA and DNA than those of PS ODNs due to their preorganized N-conformation. On the basis of the properties of these newly designed oligonucleotides, their in vitro and in vivo applications for gene silencing as true antisense oligonucleotides have been reported. In this review, antisense applications with these modified oligonucleotides are focused on.
Export Options
About this article
Cite this article as:
Koizumi Makoto, True Antisense Oligonucleotides with Modified Nucleotides Restricted in the Nconformation, Current Topics in Medicinal Chemistry 2007; 7 (7) . https://dx.doi.org/10.2174/156802607780487768
DOI https://dx.doi.org/10.2174/156802607780487768 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Diverse Models for the Prediction of Dual mTOR and PI3Kα Inhibitory Activities of Substituted 4-morpholinopyrrolopyrimidines
Letters in Drug Design & Discovery New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer
Current Pharmaceutical Design TFF (Trefoil Factor Family) Peptides and their Potential Roles for Differentiation Processes During Airway Remodeling
Current Medicinal Chemistry Multi-target Pharmacological Effects of Platycodin D
Mini-Reviews in Organic Chemistry Discovery and Development of Topoisomerase Inhibitors as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Radiosensitization of Prostate Cancer by Soy Isoflavones
Current Cancer Drug Targets Neuroendocrine Tumors of the Lung: Hystological Classification, Diagnosis, Traditional and New Therapeutic Approaches
Current Medicinal Chemistry Smart Drug-Delivery Systems for Cancer Nanotherapy
Current Drug Targets Biological Interfacial Engineering for Metastatic Cancer Diagnosis and Intervention
Current Medicinal Chemistry Determining Concentrations of Icotinib in Plasma of Rat by UPLC Method with Ultraviolet Detection: Applications for Pharmacokinetic Studies
Current Pharmaceutical Analysis Antiangiogenic Therapy
Current Pharmaceutical Design Glyoxalase 1 and 2 Enzyme Inhibitory Activity of 6-Sulfamoylsaccharin and Sulfocoumarin Derivates
Letters in Drug Design & Discovery Fluoroquinolones Prophylaxis of Bacterial Infections in Neutropenic Patients: Time to Re-Evaluate
Current Cancer Therapy Reviews Cannabis Phenolics and their Bioactivities
Current Medicinal Chemistry Current and Future Drug Treatments for Glioblastomas
Current Medicinal Chemistry A Review on CRISPR-mediated Epigenome Editing: A Future Directive for Therapeutic Management of Cancer
Current Drug Targets The Role of the RhoA/rho-kinase Pathway in Pulmonary Hypertension
Current Drug Discovery Technologies Mechanism of Action of Limonene in Tumor Cells: A Systematic Review and Meta-Analysis
Current Pharmaceutical Design Advancements in Adjuvanticity of Bioactive Inorganic and Organic Compounds
Endocrine, Metabolic & Immune Disorders - Drug Targets Medicinal Potential of Heterocyclic Compounds from Diverse Natural Sources for the Management of Cancer
Mini-Reviews in Medicinal Chemistry