摘要
在过去的几十年,由于他们的良好的分子易变性,不同类型酸磷酸核苷轭化物得到广泛研究,其拥有有趣的氢化水解机制,作为聚合酶基质识别,特别是他们作为抗病毒/抗癌治疗的开发。前几年,发现和开发了抗病毒轭合物,如磷酸核苷和亚磷酰胺,并且该领域的前辈对其进行了总结。本文中,我们将会对一些典型结构类型的基本化学和生物原理进行讨论。我们总结了最近一些类似物当中的化学和生物特性,这些类似物由我们实验室和其他人合成和评估。这包括他们作为聚合酶直接基质的新应用原理、核碱基依赖的催化和抗病毒活性,以及一种靶向给药特定组织/器官的似乎合理的“一种先导药物的先导药物”方案。
关键词: 先导药物,传递,稳定性,聚合酶,亚磷酰胺
Current Medicinal Chemistry
Title:Nucleoside Phosphate-Conjugates Come of Age: Catalytic Transformation, Polymerase Recognition and Antiviral Properties
Volume: 22 Issue: 34
Author(s): Elisabetta Groaz and Piet Herdewijn
Affiliation:
关键词: 先导药物,传递,稳定性,聚合酶,亚磷酰胺
摘要: Over the past few decades, different types of nucleoside phosphate-conjugates have been under extensive investigation due to their favorable molecular lability with interesting catalytic hydrolysis mechanisms, recognition as polymerase substrates, and especially for their development as antiviral/ anticancer protide therapeutics. The antiviral conjugates such as nucleoside phosphoesters and phosphoramidates that were discovered and developed in the initial years have been well reviewed by the pioneers in the field. In the present review, we will discuss the basic chemical and biological principles behind consideration of some representative structural classes. We will also summarize the chemical and biological properties of some of the more recent analogues that were synthesized and evaluated in our laboratory and by others. This includes new principles for their application as direct substrates of polymerases, nucleobasedependent catalytic and antiviral activity, and a plausible ‘prodrug of a prodrug’ strategy for tissue/organ-specific targeted drug delivery.
Export Options
About this article
Cite this article as:
Elisabetta Groaz and Piet Herdewijn , Nucleoside Phosphate-Conjugates Come of Age: Catalytic Transformation, Polymerase Recognition and Antiviral Properties, Current Medicinal Chemistry 2015; 22 (34) . https://dx.doi.org/10.2174/092986732234151119155207
DOI https://dx.doi.org/10.2174/092986732234151119155207 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
- 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
-
Metabolism-Directed Optimisation of Antithrombotics: The Prodrug Principle
Current Pharmaceutical Design Novel Anticancer Agents and Targets: Recent Advances and Future Perspectives
Mini-Reviews in Medicinal Chemistry Conjugates of Cell Adhesion Peptides for Therapeutics and Diagnostics Against Cancer and Autoimmune Diseases
Current Topics in Medicinal Chemistry Natural Sirtuin Modulators in Drug Discovery: A Review (2010 -2020)
Current Medicinal Chemistry Estrogens as Potential Therapeutic Agents in Multiple Sclerosis
Central Nervous System Agents in Medicinal Chemistry Mitochondrial MMP Activation, Dysfunction and Arrhythmogenesis in Hyperhomocysteinemia
Current Vascular Pharmacology Whole Embryo Culture: An Important Tool in Developmental Toxicology Today
Current Pharmaceutical Design Melatonin, a Potential Therapeutic Agent for Smooth Muscle-Related Pathological Conditions and Aging
Current Medicinal Chemistry Cardiovascular Disease and Dyslipidemia: Beyond LDL
Current Pharmaceutical Design Genetic Mechanisms and Aberrant Gene Expression during the Development of Gastric Intestinal Metaplasia and Adenocarcinoma
Current Genomics Renal COX-2, Cytokines and 20-HETE: Tubular and Vascular Mechanisms
Current Pharmaceutical Design The Importance of Alkynyl Chain Presence for the Activity of Adenine Nucleosides/Nucleotides on Purinergic Receptors
Current Medicinal Chemistry Neurotrophin-3 Stimulates Migration of Mesenchymal Stem Cells Overexpressing TrkC
Current Medicinal Chemistry Targeting Vascular Niche by Parathyroid Hormone
Current Medicinal Chemistry Chemical Constituents of Plants from the Genus Forsythia
Mini-Reviews in Organic Chemistry Multiple Means by Which Nitric Oxide can Antagonize Photodynamic Therapy
Current Medicinal Chemistry Tocotrienols and Cardiovascular Health
Current Pharmaceutical Design Essential Roles of Toll-Like Receptors in Atherosclerosis
Current Medicinal Chemistry Synthetic and Application Perspectives of Azapodophyllotoxins: Alternative Scaffolds of Podophyllotoxin
Current Medicinal Chemistry The Proteolytic Activation of Angiogenic and Lymphangiogenic Growth Factors in Cancer – Its Potential Relevance for Therapeutics and Diagnostics
Current Medicinal Chemistry